Anomeric derivatives of monosaccharides

ABSTRACT

A compound of formula (I),  
                 
wherein, n is 0 or 1; R6 and R7 are hydrogen, or together form a carbonyl oxygen; R1 is selected from the group consisting of hydrogen; —N(Z)Y and —C(Z)Y wherein; when R1 is —N(Z)Y, then: Y is selected from hydrogen, or the following, where G denotes the point of connection to the nitrogen atom in N(Y)Z (i-v); Z is selected from hydrogen or X1; Q is selected from hydrogen or W; the groups W are independently selected from the group consisting of alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl of 1 to 20 atoms, the groups X1 are independently selected from the group consisting of alkyl, alkenyl, alkynyl, heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl of 1 to 20 atoms, when R1 is —C(Z)Y, then: Y is selected from the group consisting of two hydrogen atoms, a double bonded oxygen to form a carbonyl, and a triple bonded nitrogen to form a nitrile, Z is absent, or is selected from hydrogen or U, wherein U is selected from the group consisting of alkyl, alkenyl, alkynyl, heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl of 1 to 20 atoms, when R1 is H, at least two of the groups R2, R3, R4 and R5 are selected from the group consisting of —OX2 or —N(T)Y, and the others are independently selected from hydrogen, —OH, —OX2, —N(T)Y, wherein Y is as defined above, T is selected from hydrogen or X2; and X2 is independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms, When R1 is N(Z)Y or C(Z)Y, at least one of the groups R2, R3, R4 and R5 are selected from the group consisting of —OX2 or —N(T)Y, and the others are independently selected from hydrogen, —OH, —OX2, —N(T)Y, wherein Y is as defined above, T is selected from hydrogen or X2; and X2 is independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms.

FIELD OF THE INVENTION

This invention relates to methods for the preparation of combinatoriallibraries of potentially biologically active mainly monosaccharidecompounds. These compounds are variously functionalized, with a view tovarying lipid solubility, size, function and other properties, with theparticular aim of discovering novel drug or drug-like compounds, orcompounds with useful properties. The invention provides intermediates,processes and synthetic strategies for the solution or solid phasesynthesis of monosaccharides, variously functionalised about the sugarring, including the addition of aromaticity and charge, and theplacement of amino acid and peptide side chain units or isosteresthereof.

BACKGROUND OF THE INVENTION

From a drug discovery perspective, carbohydrate pyranose and furanoserings and their derivatives are well suited as templates. Each sugarrepresents a three-dimensional scaffold to which a variety ofsubstituents can be attached, usually via a scaffold hydroxyl group,although occasionally a scaffold carboxyl or amino group may be presentfor substitution. By varying the substituents, their relative positionon the sugar scaffold, and the type of sugar to which the substituentsare coupled, numerous highly diverse structures are obtainable. Animportant feature to note with carbohydrates, is that moleculardiversity is achieved not only in the type of substituents, but also inthe three dimensional presentation. The different stereoisomers ofcarbohydrates that occur naturally (examples include glucose, galactose,mannose etc, FIG. 1), offer the inherent structural advantage ofproviding alternative presentation of substituents.

The first example of a combinatorial approach employing carbohydratechemistry, was a symposium report on the design and synthesis of apeptidomimetic using a glucose scaffold in the early 1990's¹. Theresults, revealed that the glucose based structures designed as mimeticsof a potent somatostatin (SRIF) agonist acted as agonists at lowconcentration, and at high concentration became the first knownantagonists of SRIF. Although hardly the production of a library, theresults were unique.

Continuing in part the work commenced in the early 1990's, Nicolaou andco-workers began developing carbohydrate based peptido-mimeticstargeting integrins. Many integrins recognize an Arg-Gly-Asp (RGD)sequence in ligands such as fibronectin, vitronectin and fibrinogen,each binding with different affinities to the individual integrinreceptors. Through a process of rational design a number of carbohydratebased RGD mimetics were synthesized. The chemical synthesis of ninedifferent compounds by this group with very few common intermediatesrequired a considerable amount of chemical effort. It was evident fromsuch results, that in order to generate a number of different structuresin a facile manner new chemistries needed to be developed to streamlineand enable what at this stage was unfortunately a protracted and arduousmethodology.

Since 1998 researchers in the group of Kunz² have been developing anumber of carbohydrate building blocks with a similar purpose in mind.In general the building blocks that they have developed are coupled to asolid support to effect the desired chemical transformations. Thechemistry developed can be employed to achieve, like the work ofHirschmann and co-workers³, the introduction of peptidomimetic sidechains to carbohydrate scaffolds in an effort to produce glyco-basedmimetics of cyclic peptides. Admittedly, with the chemistry they havedeveloped, there are inherent limitations in the types of functionalgroups that they are able to introduce and the range of stereoisomericbuilding blocks that they are able to employ.

It is now becoming reasonably established in the art that relates to thesolid phase production of combinatorial carbohydrate based libraries,that one of five protecting groups on a carbohydrate scaffold is aprotecting group modified as a linker, so as to allow coupling of theblock to a solid support. The strategy that then follows is simple,remove a protecting group and effect coupling at the freed functionalitywith a peptidomimetic or other reagent. Remove another protecting groupand couple with the next reagent, and so on.

Following this generally accepted principle, a system has been developedthat allows the chemical synthesis of highly structurally andfunctionally diverse derivatised carbohydrate and tetrahydropyranstructures, of both natural and unnatural origin. The diversityaccessible is particularly augmented by the juxtaposition of bothstructural and functional aspects of the molecules. In order to access awide range of diverse structures, stereo-center inversion chemistry isrequired, so as to achieve non-naturally occurring and hard to getsugars in a facile manner. Other chemistries are also required thatprovide unnatural deoxy or deoxy amino derivative which impart greaterstructural stability to the drug-like target molecules. With a suite ofreagents to effect a suitable range of chemistries on a solid support,allowing such things as; wide functional diversity, highly conservedintermediates, a limited number of common building block to be required,and with suitable chemistry to allow access to unusual carbohydratestereo-representations and including access to deoxy and deoxy aminoanalogues, a methodology is then established that can create focusedlibraries for a known target, or alternatively diversity libraries forunknown targets for random screening.

Many of the traditional methods of carbohydrate synthesis have proved tobe unsuitable to a combinatorial approach, particularly because modemhigh-throughput synthetic systems require that procedures to be readilyautomatable. The compounds and processes described herein areparticularly suited to the solid and solution phase combinatorialsynthesis of carbohydrate-based libraries, and are amenable toautomation. The methods of the invention yield common intermediates thatare suitably functionalized to provide diversity in the structure of thecompounds so generated. In this way the technology described can producemany and varied compounds around the basic structure shown in FIG. 1.Using this method, it is possible to introduce varied functionality inorder to modulate both the biological activity and pharmacologicalproperties of the compounds generated.

Thus the compounds and methods disclosed herein provide the ability toproduce random or focused binatorial-type libraries for the discovery ofother novel drug or drug-like compounds, or compounds with other usefulproperties in an industrially practical manner.

It will be clearly understood that, although a number of prior artpublications are referred to herein, this reference does not constitutean admission that any of these documents forms part of the commongeneral knowledge in the art, in Australia or in any other country.

SUMMARY OF THE INVENTION

In a first aspect, the invention provides a compound of formula I

Wherein,

-   -   n is 0 or 1; the ring may be of any configuration and the        anomeric be of either the α or β configuration;    -   R6 and R7 are hydrogen, or together form a carbonyl oxygen;    -   R1 is selected from the group consisting of hydrogen; —N(Z)Y and        —C(Z)Y wherein;

When R1 is —N(Z)Y, then:

-   -   Y is selected from hydrogen, or the following, where G denotes        the point of connection to the nitrogen atom in N(Y)Z;    -   Z is selected from hydrogen or X1;    -   Q is selected from hydrogen or W;

The groups W are independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20atoms which is optionally substituted, branched and/or linear. Typicalsubstituents include but are not limited to OH, NO, NO₂, NH₂, N₃,halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid;

The groups X1 are independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkylor heteroarylalkyl of 1 to 20 atoms which is optionally substituted,branched and/or linear. Typical substituents include but are not limitedto OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy,aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester,carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate, hydroxamic acid;

When R1 is —C(Z)Y, then:

-   -   Y is selected from hydrogen, double bond oxygen (═O) to form a        carbonyl, or triple bond nitrogen to form a nitrile.    -   Z may be optionally absent, or is selected from hydrogen or U,

Wherein U is independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl or heteroarylalkylof 1 to 20 atoms which is optionally substituted, branched and/orlinear. Typical substituents include but are not limited to OH, NO, NO₂,NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nftrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid;, heteroaryloxy, aminoalkyl,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, whichmay optionally be further substituted.

Suitably, When R1 is H, at least two of the groups R2, R3, R4 and R5 areselected from the group consisting of —OX2 or —N(T)Y, and the others areindependently selected from hydrogen, —OH, —OX2, —N(T)Y, wherein Y is asdefined above, T is selected from hydrogen or X2; and X2 isindependently selected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl,heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms,

When R1 is N(Z)Y or C(Z)Y, at least one of the R2, R3, R4 and R5 areselected from the group consisting of —OX2 or —N(T)Y, and the others areindependently selected from hydrogen, —OH, —OX2, —N(T)Y, wherein Y is asdefined above, T is selected from hydrogen or X2; and X2 isindependently selected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl,heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms,

It is understood that the rules of molecular stoichiometry will beupheld by the default addition of hydrogens atoms as required.

The groups Z and Y may be combined to form a monocyclic or bicyclic ringstructure of 4 to 10 atoms. This ring structure may be furthersubstituted with X groups;

The groups R2, R3, R4 and R5 are independently selected from hydrogen,OH, NHDde, NHDTPM and other vinylogous amines, N(Z)Y, wherein N(Z)Y isas defined above, OX and X is independently selected from alkyl,alkenyl, alkynyl, heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy,heteroaryloxy, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl orthioheteroaryl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl,arylalkyl or heteroarylalkyl of 1 to 20 atoms which is optionallysubstituted, branched and/or linear. Typical substituents include butare not limited to OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F,nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid,carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl,heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl,aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate,sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,hydroxamic acid;

With the proviso that when R2 is N(Z)Y, R6 and R7 are hydrogen, and R4and R5 are OH or together form a benzylidene or substituted benzylidene,then R1 cannot be N(Z)Y.

A preferred embodiment of this aspect provides for compounds of formulaI in which R1 is H and R4 is N

In a particularly preferred embodiment R1 is H and R4 is N(Z)Y wherein Zis hydrogen;

A further embodiment of the first aspect provides for compounds offormula I in which R1 and R4 are independently N(Z)Y;

Another embodiment provides for compounds of formula I in which R1 is Hand both R2 and R4 are N(Z)Y;

In a preferred embodiment provides for compounds of formula I in whichthe ring is of the gluco, galacto or allo configuration;

A further embodiment provides for compounds of formula I in which R1 isN(Z)Y and R2 is N(Z)Y;

A further embodiment provides for compounds of formula I in which R1 isP(Z)Y and R2 is N(Z)Y, wherein P is carbon and Y is hydrogen.

A further embodiment provides for compounds of formula I in which R1 isP(Z)Y and R4 is N(Z)Y, wherein P is carbon and Y is hydrogen.

A further embodiment provides for compounds of formula I in which R1 isN(Z)Y and R5 is N(Z)Y and the ring is of the furan form.

In a second aspect, the invention provides for a method of synthesis ofcompounds of formula I in which R1 is hydrogen, comprising the step ofreducing a synthetic intermediate of formula II, in which thesubstituent V is either bromine or chlorine, R6 and R7 are as defined inthe first aspect, R5, R4, R3, and R2 are independently selected from OH,O-acyl, N₃, NHDde, NHDTPM, NHZ, NHBOC, phthalimide, O-protecting groupor when R6 and R7 together a carbonyl oxygen, R5 may additionally beoptionally substituted O-ylalkyl or O-aryl. Where the protecting groupsmay be chosen from any suitable oxygen protecting groups known in theart, including acetals and ketals which protect two adjacent oxygens.

In a third aspect, the invention provides for a method of synthesis ofcompounds of formula I in which R1 is N(Z)Y comprising the step ofreacting a compound of formula II with and azide nucleophile, in whichthe substituents for formula II are as described in the second aspect.

In a fourth aspect, the invention provides for a method of combinatorialsynthesis of compounds of the formula I comprising the step ofimmobilizing a compound of formula III onto a support. Said support maybe soluble or insoluble. Non-limiting examples of insoluble supportsinclude derivatised polystyrene, tentagel, wang resin, MBHA resin,aminomethylpolystyrene, rink amide resin etc. Non-limiting examples ofsoluble supports include DOX-mpeg, polyethylene glycol etc.

Wherein R1 is as defined in the first aspect, R2, R3, R4, R5, R6 and R7are as defined in the second aspect, and the linkage between thecompound of formula III and the support is through any of positions R2,R3,R4 or R5.

In a fifth aspect, the invention provides for a method of synthesis ofcompounds of formula I in which R1 is N(Z)Y, comprising the step ofreacting a compound of formula IV in the presence of a lewis acid withan azide source.

in which the substituent V is —OAcyl, R6 and R7 are as defined in thefirst aspect, R4, R3, and R2 are independently selected from OH, O-acyl,N₃, NHDde, NHDTPM, NHZ, NHBOC, phthalimide, O-protecting group or whenR6 and R7 together for a carbonyl oxygen, R4 may additionally beoptionally substituted O-alkyl, O-arylalkyl or O-aryl. Where theprotecting groups may be chosen from any suitable oxygen protectinggroups known in the art, including acetals and ketals which protect twoadjacent oxygens.

In a sixth aspect, the invention provides for a method of synthesis ofcompounds of formula I in which R1 is H, comprising the step of reducinga compound of formula IV in which the substituents for formula II are asdescribed in the fifth aspect.

In a seventh aspect, the invention provides for a method ofcombinatorial synthesis of compounds of formula I comprising the step ofimmobilizing a compound of formula V onto an support. Said support maybe soluble or insoluble. Non-limiting examples of insoluble supports inthe derivatised polystyrene, tentagel, wang resin, MBHA resin,aminomethy styrene, rink amide resin etc., Non-limiting examples ofsoluble supports include DOX-mpeg, polyethylene glycol etc.

Wherein R1 is as defined in the first aspect, R2, R3, R4, R6 and R7 areas defined in the fifth aspect, and the linkage between the compound offormula V and the support is through any of positions R2, R3, or R4.

In a eighth aspect, the invention provides for a method of solutionphase combinatorial synthesis of compounds of formula I comprising thestep of alkylating a free hydroxyl on a compound of formula III, whereinR1 is as defined in the first aspect, R2, R3, R4, R5, R6 and R7 are asdefined in the second aspect and any one of the protecting substituentsmay be removed prior to alkylation.

Compounds of the invention are useful in screening for biologicalactivity.

For the purposes of this specification it will be clearly understoodthat the word “comprising” means “including but not limited to”, andthat the word “comprises” has a corresponding meaning.

General Solution and Solid Phase Methods For Examples 1-21

General Method 1: Formation of a Glycosyl Bromide

To a solution of the anomeric-acetate compound (100 mmol) indichloromethane (250 mL) at 0° C., was added a solution of 33% HBr inacetic acid (100 mL). The solution was then stirred for 2 h at roomtemperature. At this time chloroform was added to the suspension and theresulting solution poured onto ice/water. The chloroform layer was thencollected and washed with cold water, saturated sodium hydrogencarbonate, brine, dried (MgSO₄), and the solvent removed to leave afoam. This foam was trituated with ether (50 mL) for 30 min and theresulting solid filtered to give the glycosyl bromide as a white solid.Yield typically greater than 95%.

General Method 2: Reduction at the Anomeric Centre to Form a Glycitol

To a suspension of glycosyl bromide (100 mmol) in dry toluene 200 mL wasadded tributyltin hydride (110 mmol) and the whole refluxed undernitrogen for 3 h. The suspension was concentrated to dryness and theresidue re-dissolved in a 2:1 dichloromethane/chloroform (250 mL)mixture. To the residue was then added potassium fluoride (20 g) inwater (100 mL), and the heterogeneous solution stirred vigorously for 45min. The resulting suspension was filtered through a pad of celite andwashed several times with dichloromethane. The combined filtrates werethen washed with water, brine, dried (MgSO₄), and solvent removed invacuo to leave a solid in typically quantitative yield.

General Method 3: Solution Phase Zemplen

To a suspension of the acetylated compound (100 mmol) in dry methanol(125 mL) at 0° C. was added a solution of sodium methoxide (0.33 mmol)in dry methanol (125 mL) and the mixture was stirred under nitrogen for2 h. Amberlite IR 120 H⁺ was added until pH 5 was reached, the solutionwas filtered and the resin washed several times with a 2:1methanol/dichloromethane mixture. The combined filtrates were thenconcentrated to dryness to leave a solid. Typically quantitave yield.

General Method 4: Solution Phase Benzylidene Protection

To a solution of the triol (˜100 mmol) in dry N,N-dimethylformamide (325mL)/acetonitrile (200 ml) was added 4-methoxybenzaldehyde dimethylacetal (180 mmol) and p-toluene sulfonic acid (2.5 mmol). This solutionwas then heated at 60° C. on a rotary evaporator at 300 mmHg for 30 minand then over the course of 4 h the pressure was reduced to 80 mmHg andapproximately 200 mL of solvent collected. After this time a secondbatch of reagent (70 mmol) and acetonitrile (125 mL) was added and theevaporation process repeated over 2 h. All solvent was then removedunder reduced pressure and the residue re-dissolved in an 8:1chloroform/triethylamine mixture, washed with dilute sodium hydrogencarbonate, dried (MgSO₄) and the solvent removed under reduced pressureto leave a oil. The oil was typically loaded onto a pad of silica andeluted with ˜10% ethyl acetate in light petroleum (40-60° C.), toprovide a white solid.

General Method 5: Solution Phase Benzoylation

The sugar (100 mmol) was partially suspended in pyridine (400 mL) andp-chlorobenzoyl chloride (46 mL, 120 mmol) added dropwise at 0° C. andthe resulting reaction mixture stirred at room temperature for 2 h.After this time cold water (30 mL) was added and the solution stirredfor a further 1 h at room temperature. All solvents were then removedunder reduced pressure and any traces of pyridine azeotropically removedwith toluene. The residue solid was then redissolved in chloroform andwashed with water, 10% citric acid, saturated sodium hydrogen carbonate,brine, dried (MgSO₄) and concentrated under reduced pressure to leave afoam. This foam was trituated with ether and the resulting solidfiltered to give the benzoylated compound as a solid, typical yield·85%.

General Method 6: Solution Phase Nucleophilic Inversion of a CarbonCentre

To a solution of the sugar (100.0 mmol) in dry chloroform (300 mL)cooled to −20° C., was added pyridine (180.0 mmol) and trifluoromethanesulfonic anhydride (115 mmol) and the whole stirred for 1 h at thistemperature. The reaction was then diluted with chloroform, and theresulting solution washed with cold water, cold 10% hydrochloric acid,cold water, dried (MgSO₄), and the solvent removed in vacuo. Theresulting residue was then redissolved in N,N-dimethylformamide (600mL), and sodium azide (500 mmol) was added at 0° C. in portions. Thesuspension stirred overnight at room temperature. The reaction wasdiluted with chloroform and the resulting solution then washed withwater, 10% citric acid, saturated sodium hydrogen carbonate, brine,dried (MgSO₄), and the solvent removed in vacuo, followed by azeotropingwith toluene to leave the product, typically 95% yield.

General Method 7: Solution Phase Alkylation

To a suspension of sodium hydride (100 mmol) in dryN,N,-dimethylformamide (360 mL) at 0° C. under nitrogen was added asolution of the sugar (63.2 mmol) in dry N. N-dimethylformamide (30 mL).The mixture was stirred at 0° C. for 15 min and then warmed to roomtemperature and stirred for a further 30 min. The suspension was againcooled to 0° C., the alkylating agent (85 mmol) added dropwise over aperiod of 5 min, after which the suspension was warmed to roomtemperature and stirred for 16 h. The suspension was then cooled to 0°C. and the reaction quenched with ammonium chloride solution, chloroformadded, and the organic layer washed with saturated sodium hydrogencarbonate, water, dried (MgSO₄) and all solvent removed to leave an oil.Crude products were purified by column chromatography (typically:silica, 50% ethyl acetate in light petroleum (40-60° C.)) to give thedesired product as a solid, in yields of 55-95%.

General Method 8: Solution Phase DTPM Removal

To a solution of the DTPM derivatised sugar (100 mmol) in a 3:1 mixtureof dry methanol/N,N,-dimethylformamide (500 mL), was added hydrazinemonohydrate (350 mmol) and the mixture stirred for 3 h. After this timethe mixture was filtered and the filtrate was then concentrated underreduced pressure. The residue was redissolved in dichloromethane, washedwith saturated sodium chloride, dried (MgSO₄) and all solvent removedunder reduced pressure to leave a solid, typically in quantitativeyield.

General Method 9: Solution Phase HBTU Coupling

To a solution of the acylating agent (10 mmol) and HBTU (12 mmol) in dryN,N,-dimethylformamide (60 mL) was added diisoproplyethylamine (25 mmol)and the mixture stirred for 10 min. A solution of the sugar buildingblock (9.4 mmol) in dry N,N,-dimethylformamide (8 mL), was then addedand the mixture further stirred for 16 h. Chloroform was then added andthe reaction mixture was washed with water, 10% citric acid, saturatedsodium hydrogen carbonate, brine, dried (MgSO₄) and the solvent removedunder reduced pressure to leave an oil. Purification of the products wasby column chromatography (typically, silica; 50% ethyl acetate in lightpetroleum (40-60° C.)), or alternatively by trituation with diethylether to give clean products in typical yields of 55-85%.

General Method 10: Solution Phase Reaction with an Isocyanate

To a solution of the sugar derivative (10 mmol) in dry dichloromethane(100 mL) was added dropwise ethyl isocyanatoacetate (10.7 mmol). Theresulting solution stirred for 3 h. In the case of a precipitateoccuring, the solid was filtered after 3 h and washed withdichloromethane to give a white solid. Alternatively if no precipitateformed, chloroform was added and the reaction mixture washed with water,dried (MgSO₄) and the solvent removed in vacuo to typically leave anoil. Purification of oils was achieved by column chromatography.Products were typically formed in yields of 65-90%.

General Method 11: Solution Phase Reaction with an Anhydride

To a solution of the sugar derivative (10 mmol) in dry dichloromethane(90 mL) was added dropwise acetic anhydride (11 mmol). The resultingsolution stirred for 16 h. In the case of a precipitate occuring, thesolid was filtered after and washed with dichloromethane to yield awhite solid. Alternatively if no precipitate occured, chloroform wasadded and reaction mixture washed with water, 10% citric acid, saturatedsodium hydrogen carbonate, brine, dried (MgSO₄) and the solvent removedunder reduced pressure to leave an oil. Oils were purified by columnchromatography. Products were typically formed in yields of 50-99%.

General Method 12: Solution Phase Reaction with an Acid Chloride

To a solution of the sugar derivative (10 mmol) in dichloromethane (100mL) was added diisopropylethylamine (12 mmol) and an acid chloride (11.6mmol), and the solution then stirred for 16 h. Chloroform was then addedand the reaction mixture washed with water, 10% citric acid, saturatedsodium hydrogen carbonate, brine, dried (MgSO₄) and the solvent removedunder reduced pressure to give an oil. Purification was by either columnchromatography (typically: silica; 50% ethyl acetate in light petroleum(40-60° C.)), or by trituation with diethyl ether. Products weretypically formed in yields of 70-80%.

General Method 13: Solution Phase Reduction of an Azide

To a stirred solution of the sugar derivative (10 mmol) in methanol (90mL) was a solution of ammonium chloride (50 mmol) in water (18 mL).Added to the reaction mixture was zinc dust (300 mmol) and the resultingsuspension stirred for 3 h. The reaction mixture was then filteredthrough a pad of celite and washed with ethyl acetate. The organic layerwas then collected, washed with saturated sodium hydrogen carbonate,dried (MgSO₄) and all solvent removed under reduced pressure to leave awhite solid. Products were typically formed in yields of 60-75%.

General Method 14: Solution Phase Removal of p-Methoxybenzyl Group

Sugar derivative (˜2 mmol) was dissolved in a solution of 70%chloroform, 20% trifluoroacetic acid, 5% anisole, 5% water, and theresulting reaction mixture stirred for 6 h. All solvent was then removedunder reduced pressure to leave a dark oil. Products were purified byHPLC-MS

General Method 15: Solution Phase Base Catalysed Hydrolysis

Sugar derivative (˜2 mmol) was dissolved in methanol (˜1.5 mL). To thissolution was 1M sodium hydroxide (0.42 mL) and the resulting reactionmixture agitated for 16 h. Amberlite resin (400 mg) was added, thesuspension was then stirred for 30 sec, filtered, and resin washed withmethanol. The resulting solutions were collected and freeze dried, andthe residues then purified by HPLC-MS.

General Method 16: Simultaneous Removal of Benzoate and DTPM

Sugar derivative (1 mmol) was stirred at room temperature in a 1 molarNaOH/methanol solution (6 mL, 1.5 mmol) in DMF (1.5 ml) until completeconsumption for (12 hrs). Hydrazine monohydrate (0.3 ml) was added andthe stirring continue for 2 hr. The volatile solvents were removed invacuo and the residue was taken up in EtOAc and washed with saturatedbicarbonate solution, dried over MgSO₄, and evaporated to dryness.Products were typically formed in yields of 85-90%.

General Method 17: Solution Phase Diazotransfer

To a solution of the sugar derivative (1 mmol) and CuSO₄.5H₂O (0.02mmol) in methanol/water (5:1, 10 mL), was added drop-wise the TfN₃solution (˜4.5 mmol). The reaction mixture was stirred at roomtemperature for 20 hr and more TfN₃ (˜1.4 mmol) was added. Afteradditional 16 hr, concentrated NH₄OH solution was added to quench excessTfN₃ and the stirring continued for 72 hr. The phases were separated andthe aqueous phase was extracted with dichloromethane. The combinedorganic layers were washed with saturated bicarbonate solution, driedover MgSO₄ and evaporated to dryness. The residue was evaporated toafford the desired product in quantitative yield.

General Method 18: Solution Phase Benzylidene Removal

To a solution of the sugar derivative (1 mmol) inacetonitrile/methanol/water (1:1:0.1), was added TsOH.H₂O (˜100micromol). The resulting reaction mixture was stirred at 50° C. for 1.5hrs. The volatile solvents were then removed in vacuo and the residuepurified by flash chromatography. The desired product was typicallyobtained in 70-80% yield.

General Method 19: Solution Phase Silyl Protection.

To a solution of the sugar derivative (1 mmol) in pyridine (1ml), wasadded DMAP (1 mmol) and TBDPSCI (1.5 mmol). The resulting reactionmixture was stirred at 120° C. for 45 min, then the solvent removed invacuo. The residue was taken up in dichloromethane washed with 1 N HClsolution, dried over MgSO₄ and evaporated to dryness. The residue waschromatographed to afford the desired product in typically 85-95% yield.

General Method 20: Coupling of Building Block to Resin

The Trichloroacetimidate derivatised resin (IRORI Wang resin ˜1 mmol)was weighed into the reaction vessel and washed with THF. Thederivatised building block (1.86 mmol) was dissolved in anhydrous DCM(1.2 ml), added to the resin and shaken for 3 mins. BF₃.Et₂O (˜100 μl)was added and the reaction vessel shaken continuously for 10 mins. Thereaction mixture was filtered under vacuum and the resin washed withTHF, DCM, and dried.

General Method 21: Solid Phase Debenzoylation

The resin bound sugar was shaken in a solution of THF/MeOH (5:1) andNaOMe (0.02 Molar) overnight. The reaction was drained and washed withanhydrous THF and repeated as described above. The reaction solvent wasdrained and the resin washed with THF, a solution of THF: CH₃COOH: MeOH8:1:1, THF, and DCM. The resin was dried overnight.

General Method 22: Solid Phase Alkylation

The resin was reacted with a 0.25 molar solution of tert-butoxide in DMF(5 min) and then the alkylating agent, (0.25 molar in DMF, 20 min) wasreacted with the resin. The resin was washed with DMF and again treatedwith the two solutions, this procedure was repeated a further fourtimes. The final wash of the resin was performed as above; with DMF,THF/MeOH/CH₃CO₂H (8:1:1), THF, DCM and MeOH. The resin was then driedovernight.

General Method 23: Solid Phase Silyl Deprotection

A solution of PSHF (proton sponge hydrogen fluoride) (0.5 Molar inDMF/Acetic Acid, 95:5) was prepared. The resin was added to the solutionand the reaction was stirred at 65° C. for 24 hours. The resin was thenwashed with DMF, MeOH/CH₃COOH/THF, 1:1:8, THF and DCM, and then driedunder high vacuum

General Method 24: Solid Phase Azide Reduction

Resin was placed in a round bottom flask. A solution of tert-Butoxide(0.2 molar) in anhydrous DMF was prepared. DTT (0.2 molar) was added tothe tert-Butoxide solution and stirring continued until all DTTdissolved. The solution was poured into the Buchner flask containing theKans. The reactor was degassed by applying vacuum (15 mbar) and filledwith nitrogen. This technique was repeated twice and the reactor shakenat room temperature for 6 hr, allowing the evolved N₂ gas to escape. Thereaction solvent was removed from the flask and the Kans washed withDMF, THF, and MeOH before being dried under high vacuum for 12 hours.

General Method 25: Solid Phase N-Acylation

Method 1

Acids were weighed into round bottom flask and DIC(diisopropylcarbodiimide) (0.25 molar) in DMF was added to make a 0.5molar solution of the acid. The resultant solution was stirred at roomtemperature for 1 hour and DMAP (to 0.05 molar) was added. The solutionwas poured into a reactor containing the Kans and shaken vigorously. Thereactor was degassed by applying vacuum (15 mbar) and filled withnitrogen. This technique was repeated twice and the reactor shaken atroom temperature over night. The reaction solvent was removed from theflask and the Kans washed with DMF, MeOH, THF, MeOH, DCM and MeOH.

Method 2:

Acids were weighed into round bottom flask and DMF was added to make a0.5 M solution, followed by addition of DIPEA (to make 0.5 M). Thesolution was stirred until homogeneous and HBTU (to make 0.5 M) wasadded. Stirring was continued for additional 30 minutes and the solutionwas poured into a reactor containing the Kans and shaken vigorously. Thereactor was degassed by applying vacuum (15 mbar) and filled withnitrogen. This technique was repeated twice and the reactor shaken atroom temperature for overnight. The reaction solvent was removed fromthe flask and the Kans washed with DMF, MeOH, THF, MeOH, DCM and MeOH.

General Method 26: Solid Phase Nitro Group Reduction

A solution of tin(II) chloride (1 Molar) in a mixture of DMF and waterwas prepared, filtered, the solution was poured into a reactorcontaining the Kans and shaken vigorously. The reactor was degassed byapplying vacuum (15 mbar) and filled with nitrogen. This technique wasrepeated twice and the reactor shaken at room temperature for 24 hour.The Kans were washed with DMF, THF, DCM, MeOH and DCM and dried underhigh vacuum.

General Method 27: Solid Phase Fmoc Removal

A 20% v/v solution of piperidine in DMF was prepared and the solutionwas poured into a reactor containing the Kans and shaken vigorously. Thereactor was degassed by applying a vacuum (15 mbar) and then was filledwith nitrogen. This technique was repeated twice and the reactor shakenat room temperature for one hours. After one hour the solvent wasremoved, the Kans were washed with DMF and the deprotection was repeatedas above. The reaction solvent was removed, the Kans washed with DMF,MeOH, THF, MeOH, DCM and MeOH and dried under high vacuum.

General Method 28: Solid Phase Guanylation

A solution of 3,5-dimethylpyrazolyl formamidinium nitrate (0.2 molar) inanhydrous DMF was prepared, and DIPEA (to 1 molar) added. The resin inKans were pooled, added to the solution, and the reaction was stirred at65° C. for 24 hours. The reaction solvent was removed from the flask viaa vacuum line and the flask shaken to release further solvent from theKans. The Kans were washed with DMF, THF and DCM and dried under highvacuum.

General Method 29: Cleavage from Resin

Cleaving solutions were prepared from DCM (60%), triethylsilane (20%),TFA (20%). The Kans were opened and the resins poured into reactors inthe MiniBlock, 0.7 ml of the above cleaving solution was added to eachreactor and the reactors were shaken at room temperature for 3 hours.The solutions were collected into test tubes (12×75 mm). The resins werewashed with DCM. The washings were combined with the cleavage in thetest tubes and the volatile solvents were removed by beta RVC. Theresidues were dried in the vacuum oven for 48 hours. Analytical sampleswere obtained by washing the remaining resins with acetonitrile (0.5ml), collected in 96-wells plate and evaporated in alpha RVC. Thesamples were re-dissolved in acetonitrile and analysed.

General Method 30: DTPM Protection of an Amine

To a stirred solution of the amino compound (20 mmol) dissolved in MeOH(150 mL) at room temperature was added a solution of DTPM reagent (20mmol) in MeOH (50 mL). After 10 min the product started to crystalliseand after 40 mins the reaction mixture was filtered. The crystallineresidue was washed with ether and dried under vacuum to yield the DTPMprotected product in typically 90% yield.

General Method 31: N-Acyl Formation using Diisoproplycarbodiimide

A solution of the starting material (0.62 mmol) in dry DCM was added toa solution of the acid (0.76 mmol) and DIC (0.76 mmol) in DCM (5 mL).The reaction was stirred for 3 h and the reaction mixture then dilutedwith DCM. The reaction mixture was washed with 10% citric acid, satd.sodium bicarbonate solution, filtered over cotton and the solventsevaporated. Column chromatography of the resulting residue provided theproduct, typically in 90% to near quantitative yields.

General Method 32: Solid Phase Cleavage of the DTPM Protecting Group.

A 5% solution of hydrazine hydrate in DMF was prepared. The cleavagesolution was added to resin in a reactor (approx. 1 mL per 100 mg ofresin) and left to react for four hours. The resin was filtered, andwashed with DMF, MeOH, THF, MeOH, DCM and MeOH and then dried under highvacuum.

General Method 33: Selective Benzgyidene Ring Opening to the 6-Position.

The benzylidene protected compound (50 mmol) was dissolved in dryN,N-dimethylformamide (400 mL) and added to a flask containingpre-activated 3A molecular sieves (120 g). To this suspension was addedsodium cyanoborohydride (300 mmol) and the resulting reaction mixturestirred for 30 min under nitrogen. The suspension was then cooled to 0°C., and a solution of TFA (650 mmol) in dry N,N-dimethylformamide (80mL) added in portions, and the suspension then heated at 55° C. for 16h. The suspension was then filtered through a bed of celite and washedseveral times with chloroform. These combined washings were then washedwith water, 10% citric acid, saturated sodium hydrogen carbonate, brine,dried (MgSO₄), and the solvent removed in vacuo to leave a yellow foam,which was azeotropically dried with toluene. Typical yields were in theorder of 85-95%.

General Method 34: Formation of a Glycosyl Azide.

From the anomeric acetate derivative the glycosyl bromide was preparedas described in General Method 1. To a solution of the bromosugar (50mmol) in acetonitrile (200 mL) was added TMS-azide (100 mmol) followedby TBAF (100 mmol). The reaction mixture was left to stir for 2 hours atwhich time the solvent was removed in vacuo, the residue taken up inchloroform, and the resulting solution washed with saturated sodiumhydrogen carbonate, brine, dried (MgSO₄), and the solvent removed invacuo to leave a solid, typically in 85-95% yield.

EXAMPLE 1 Synthesis of1,5-anhydro-4-azido-3-O-(4-chlorobenzoyl)-2,4-dideoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H, 5H)-trioxopyrimidin-5-ylidene)methylamino]-6-O-(4-methoxybenzyl)-D-galactitol

1-a. Synthesis of 2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H, 3H,5H)-trioxopyrimidin-5-yildene)methylaminol-3,4,6-O-triacetyl-α-D-glucopyranosylbromide (2)

Compound 2 was synthesized according to the procedure described inGeneral Method 1. Compound 2, (96%) as a white solid.R_(f)(product)≈0.75 in ethyl acetate; δ_(H) (400 MHz; CDCl₃) 2.00 (3 H,s), 2.05 (3 H, s), 2.09 (3 H, s), 3.29 (3 H, s), 3.30 (3 H, s), 3.78 (1H, dt, J 9.9 Hz and J 3.6 Hz), 4.13 (1 H, dd, J 13.4 Hz and J 3.0 Hz),4.35 (2 H, m), 5.19 (1 H, t, J 9.8 Hz), 5.46 (1 H, t, J 9.8 Hz), 6.50 (1H, d, J4.0 Hz), 8.13 (1 H, d, J 13.6 Hz) and 10.30 (1 H, br t, J 11.6Hz); LCMS [M+H]⁺=534.

1-b. Synthesis of 1,5-anhydro-2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H, 3H,5H)-trioxopyrimidin-5-ylidene)methylaminol-3,4,6-O-triactyl-glucitol (3)

Compound 3 was synthesized according to the procedure described inGeneral Method 2. Compound 3, quantitative yield; R_(f)(product)≈0.65 inethyl acetate., δ_(H) (400 MHz; CDCl₃) 2.03 (3 H, s), 2.04 (3 H, s),2.09 (3 H, s), 3.28 (3 H, s), 3.30 (3 H, s), 3.53 (1 H, t, J 11.2 Hz),3.68 (2 H, m), 4.14 (2 H, m), 4.25 (1 H, dd, J 12.6 Hz and J 5.0 Hz),5.04 (1 H, t, J 9.4 Hz), 5.16 (1 H, t, J 9.6 Hz), 8.13 (1 H, d, J 13.6Hz) and 10.10 (1 H, br t, J 11.4 Hz); δ_(C) (400 MHz; CDCl₃) 21.04(CH₃×2), 21.17 (CH₃), 27.63 (CH₃), 28.33 (CH₃), 60.36 (CH), 62.32 (CH₃),68.29 (CH), 68.62 (CH₂), 73.98 (CH), 76.97 (CH), 92.65 (C), 151.97 (C),158.84 (CH), 162.65 (C), 164.91 (C), 169.57 (C), 170.36 (C) and 170.65(C); LCMS [M+H]⁺=456.

1-c. Synthesis of 1,5-anhydro-2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H, 3H,5H)-trioxopyrimidin-5-ylidene)methylaminol-D-glucitol (4)

Compound 3 was treated as described by General Method 3 to provide 4;R_(f)(product)≈0.00 in 1:1 ethyl acetate/light petroleum (40-60° C.),(S.M≈0.4). When system changed to 9:1 acetonitrile/methanol,R_(f)(product)≈0.4. (S.M≈1.0);, δ_(H) (400 MHz; DMSO) 3.13 (3 H, s),3.14 (3 H, s), 3.47 (3 H, m), 3.65 (3 H, dd), 3.85 (1 H, d, J 6.0 Hz),4.52 (1 H, t, J 5.8 Hz), 5.11 (1 H, d, J 4.8 Hz), 5.28 (1 H, d, J 5.6Hz), 8.18 (1 H, d, J 14.4 Hz) and 10.03 (1 H, br t, J 8.4 Hz); δ_(C)(400 MHz; DMSO) 27.63 (CH₃), 28.29 (CH₃), 62.00 (CH₂), 62.90 (CH), 67.68(CH₂), 71.37 (CH), 75.42 (CH), 82.22 (CH), 152.18 (C×2), 160.18 (CH),162.71 (C) and 164.37 (C); LCMS [M+H]⁺=330.

1-d. Synthesis of 1,5-anhydro-2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H, 3H,5H)-trioxopyrimidin-5-ylidene)methylamino]-4,6-O-(4-methoxybenzylidene)-D-glucitol(5)

Compound 4 was treated as described by General Method 4, to give thedesired product 5 as a solid (86%); R_(f)(product)≈0.1 in 1:1 ethylacetate/light petroleum (40-60° C.), δ_(H) (400 MHz; CDCl₃) 3.29 (3 H,s), 3.30 (3 H, s), 3.48 (5 H, m), 3.70 (1 H, t, J 10.2 Hz), 3.81 (3 H,s), 3.83 (1 H, m), 4.11 (1 H, m), 4.32 (1 H, dd, J 10.4 Hz and J 4.8Hz), 5.51 (1 H, s), 6.90 (2 H, d, J 8.8 Hz), 7.40 (2 H, d, J 8.4 Hz),8.24 (1 H, d, J 13.6 Hz) and 10.20 (1 H, br t, J 11.5 Hz); LCMS[M+H]⁺=448.

1-e. Synthesis of1,5-anhydro-3-O-(4-chlorobenzoyl)-2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H,5H)-trioxopyrimidin-5-ylidene)methylaminol-4,6-O-(4-methoxybenzylidene)-D-glucitol(6)

Compound 5 was treated according to General Method 5, to give theproduct 6 as a off-white solid (83%); R_(f)(product)≈0.33 in 1:1 ethylacetate/light petroleum (40-60° C.). (S.M≈0.17); δ_(H) (400 MHz; CDCl₃)3.24 (3 H, s), 3.25 (3 H, s), 3.72 (8 H, m), 4.14 (1 H, t, J 5.5 Hz),4.35 (1 H, t, J 5.4 Hz), 5.50 (1 H, s), 5.57 (1 H, t, J 9.6 Hz), 6.82 (2H, dd, J 6.6 Hz and J 2.2 Hz), 7.30 (2 H, dd, J 6.8 Hz and J 2.0 Hz),7.38 (2 H, dd, J 6.8 Hz and J 2.0 Hz), 7.93 (2 H, dd, J 6.6 Hz and J 2.2Hz), 8.12 (1 H, d, J 13.6 Hz), and 10.20 (1 H, br t, J 11.6 Hz); LCMS[M+H]⁺=586.

1-f. Synthesis of1,5-anhydro-3-O-(4-chlorobenzoyl)-2-deoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H, 5H)-trioxopyrimidin-5-ylidene)methylaminol-6-O-(4-methoxybenzyl)-D-glucitol (7)

Compound 6 was treated according to the procedure described in GeneralMethod 33 to give the product 7 as an off-white foam (93%);R_(f)(product)≈0.26 in 1:1 ethyl acetate/light petroleum (40-60° C.).(S.M≈0.33); δ_(H) (400 MHz; CDCl₃) 3.23 (3 H, s), 3.24 (3 H, s), 3.51 (2H, m), 3.80 (8 H, m), 4.13 (1 H, dd, J 11.4 Hz and J 5.4 Hz), 4.52 (2 H,q, J 11.2 Hz), 5.27 (1 H, t, J 9.6 Hz), 6.87 (2 H, d, J 8.8 Hz), 7.26 (2H, m), 7.40 (2 H, d, J 8.8 Hz), 7.93 (2 H, d, J 8.8 Hz), 8.11 (1 H, d, J13.6 Hz), and 10.30 (1 H, br t, J 11.5 Hz); LCMS [M+H]⁺=588.

1 g. Synthesis of1,5-anhydro-4-azido-3-O-(4-chlorobenzoyl)-2,4-dideoxy-2-[(1,3dimethyl-2,4,6-(1H,3H,5H)-trioxopyrimidin-5-ylidene)methylaminol-6-O-(4-methoxybenzyl)-D-galactitol(8)

Compound 7 was treated according to the procedure described in GeneralMethod 6 to give compound 8, (93%) R_(f)(product)≈0.62 in 1:1 ethylacetate/light petroleum. Product recrystallised from isopropanol; LCMS[M+H]⁺=613.

1-h. Synthesis of1,5-anhydro-4-azido-3-O-(4-chlorobenzoyl)-2,4-dideoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H, 5H)-trioxopyrimidin-5-ylidene)methylaminol-D-galactitol (9)

Compound 8 was reacted according to General Method 3, to give thedesired product 9 (70%) as a white foam, δ_(H) (400 MHz; CDCl₃) 3.25 (3H, s), 3.26 (3 H, s), 3.65 (5 H, m), 3.80 (3 H, s), 4.09 (3 H, m), 4.50(2 H, q, J 9.5 Hz and J 3.6 Hz), 6.89 (2 H, d, J 8.8 Hz), 7.26 (2 H, d,J 8.8 Hz), 8.21 (1 H, d, J 13.6 Hz), and 10.15 (1 H, br t, J 11.4 Hz);LCMS [M+H]⁺=475.

EXAMPLE 2 Synthesis of a Galactitol Library—Preparation ofIntermediates: General Procedures for Alkylation of the C-3 Position andRemoval of the DTPM Group

2-a. Alkylation of the C-3 Position: Preparation of Compounds 10, 11 and12

Compounds 10, 11, and 12 were prepared according to General Method 7.Analytical Data Compound No. 10 11 12 [M + H]⁺ 503 589 589

2-b. Removal of the DTPM Group at the C-2 Position. Preparation ofCompounds 13, 14, 15 and 16

Compounds 13, 14, 15, and 16 were prepared according to General Method8. Analytical Data. Compound 13 14 15 16 [M + H]⁺ 337 423 309 423

Data for5-Azido-4-ethoxy-6-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-3-ylamine(13)

Yellow oil, yield (100 %), δ_(H) (400 MHz; CDCl₃) 1.27 (3 H, t, J 7.0Hz), 1.50 (2 H, br s), 3.06 (1 H, t, J 11.0 Hz), 3.21 (2 H, m), 3.52 (4H, m), 3.78 (4 H, m), 3.93 (1 H, dd, J 10.8 Hz and J 4.6 Hz), 4.04 (1 H,d, J 3.2 Hz), 4.48 (2 H, q, J 14.8 Hz and J 11.6 Hz), 6.88 (2 H, d, J8.4 Hz) and 7.26 (2 H, d, J 8.8 Hz); LCMS [M+H]⁺=337.

2-c. Preparation of Intermediates: General Procedures from Preparationof Derivatives at the C-2 Position

Compounds 17 to 51 were individually prepared according to one ofGeneral Methods 9,10, 11 and 12.

Analytical Data: Example of a product of General Method 9:[3-Azido-5-(3-tert-butoxycarbonylamino-propionylamino)-2-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-4-yloxy]-aceticacid tert-butyl ester (33)

Sugar (16) (3.1 mmol) coupled to Boc-β-alanine (3.2 mmol) gave the titlecompound (33) as an off-white solid, in 69% yield after columnchromatography (silica; 50% ethyl acetate in light petroleum (40-60°C.)), δ_(H) (400 MHz; CDCl₃) 1.42 (9 H, s), 1.49 (9 H, s), 2.43 (2 H, t,J 6.4 Hz), 2.95 (1 H, t, J 10.2 Hz), 3.48 (6 H, m), 3.81 (3 H, s), 4.07(4 H, m), 4.47 (3 H, q, J 11.4 Hz and J 6.8 Hz), 5.24 (1 H, br. s.),6.89 (2 H, d, J 8.8 Hz), 7.25 (2 H, d, J 8.4 Hz) and 7.51 (1 H, br. d, J5.2 Hz); LCMS [M+H]⁺=594.

Example of a Product of General Method 9: Acetic acid[5-azido-4-hydroxy-6-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-3-ylcarbamoyl]-methylester (45)

Sugar (15) (4.2 mmol), was coupled to acetoxyacetic acid (4.3 mmol) andafter trituation with diethyl ether gave the title compound (45) as awhite solid in 64%, δ_(H) (400 MHz; CDCl₃) 2.17 (3 H, s), 3.19 (1 H, t,J 10.8 Hz), 3.44 (1 H, d, J 7.2 Hz), 3.60 (3 H, m), 3.76 (1 H, m), 3.80(3 H, s), 4.06 (3 H, m), 4.49 (2 H, q, J 10.2 Hz and J 2.4Hz), 4.56 (2H, s), 6.04 (1 H, d, J 6.8 Hz), 6.89 (2 H, d, J 6.8 Hz) and 7.26 (2 H,d, J 8.8 Hz); LCMS [M+H+Na]⁺=431.

Example of a product of General Method 9:N-[5-Azido-4-hydroxy-6-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-3-yl]-succinamicacid methyl ester (18)

Sugar (15) (4.5 mmol), coupled to succinic acid mono methyl ester (4.8mmol), after trituation with diethyl ether gave the title compound (18)(63%), as a white solid; δ_(H) (400 MHz; DMSO) 2.35 (2 H, dt, J 6.9 Hzand J 2.4 Hz), 2.47(2 H, t, J 6.8 Hz), 2.89 (1 H, t, J 10.8 Hz), 3.43(2H, dd, J 5.8 Hz and 2.6 Hz), 3.56 (3 H, s), 3.64 (2 H, dd, J 11.0 Hz andJ 5.0 Hz), 3.73 (3 H, s), 3.80 (3 H, m), 4.39 (2 H, q, J 10.9 Hz), 5.48(1 H, d, J4.4 Hz), 6.89 (2 H, dd, J6.4 Hz and J 2.8 Hz), 7.23 (2 H, d, J8.8 Hz) and 7.73 (1 H, d, J 8.0 Hz); 6c (400 MHz; DMSO) 29.65 (CH₃),30.80 (CH₃), 48.62 (CH₂), 52.12 (CH₂), 55.86 (CH₂), 63.92 (CH₂), 68.56(CH), 69.85 (CH), 72.18 (CH), 72.76 (CH), 76.20 (CH₂), 114.30 (CH×2),129.03 (CH×2), 130.68 (C), 159.32 (C), 171.73 (C) and 173.35 (C); LCMS[M+H+Na]⁺=423.

Example of a product of General Method 10;{3-[5-Azido-4-hydroxy-6-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-3-yl]-ureido}-aceticacid ethyl ester (41)

Compound 41, white solid, yield 66%; δ_(H) (400 MHz; DMSO) 1.17 (3 H, t,J 6.8 Hz), 2.88 (1 H, t, J 10.6 Hz), 3.31 (2 H, s), 3.42 (2 H, m), 3.67(9 H, m), 3.85 (1 H, dd, J 3.2 Hz and J 1.2 Hz), 4.06 (2 H, q, J 7.0Hz), 4.39 (2 H, q, J 10.7 Hz), 5.56 (1 H, d, J 4.4 Hz), 6.09 (1 H, d, J6.8 Hz), 6.28 (1 H, t, J 5.8 Hz), 6.89 (1 H, d, J 6.8 Hz) and 7.22 (1 H,d, J 6.8 Hz); δ_(C) (400 MHz; DMSO) 15.03 (CH₃), 42.28 (CH₂×2), 49.30(CH₃), 55.88 (CH), 61.00 (CH₂), 64.13 (CH), 69.47 (CH₂), 69.84 (CH₂),72.74 (CH), 76.06 (CH), 114.30 (CH×2), 129.03 (CH×2), 130.68 (C), 158.56(C), 159.32 (C) and 171.57 (C); LCMS [M+H]⁺=438.

Example of a product of General Method 11:[5-Acetylamino-3-azido-2-(4-methoxy-benzyloxy-methyl)-tetrahydro-pyran-4yloxy]-aceticacid tert-butyl ester (36)

Derivatisation of the t-butyl sugar (16) (3.1 mmol) gave the titlecompound 36 as a yellow oil, 89%, δ_(H) (400 MHz; CDCl₃) 1.43 (9 H, s,C(CH₃)₃), 1.94 (3 H, s), 2.88 (1 H, t, J 10.0 Hz), 3.45 (4 H, m), 3.74(3 H, s), 4.04 (4 H, m),4.40 (3 H, m), 6.82 (2 H, d, J 8.8 Hz), 7.19(2H, d, J 8.8 Hz) and 7.41 (1 H, br d, J 5.2 Hz); LCMS [M+H]⁺=465.

Example of a product of General Method 12:3-[3-Azido-2-(4-methoxy-benzyloxymethyl)-5-(2-methoxycarbonyl-acetylamino)-tetrahydro-pyran-4-yloxy]-2,2-dimethyl-propionicacid methyl ester (51)

Derivatisation of the pivolate sugar (14) (3.6 mmol) gave the titlecompound as a brown oil (51) 75%; δ_(H) (400 MHz; CDCl₃) 1.16 (3 H, s),1.24 (3 H, s), 3.35 (3 H, m), 3.57 (6 H, m), 3.68 (3 H, s), 3.73 (3 H,s), 3.81 (3 H, s), 4.28 (3 H, m), 4.46 (2 H, q, J 12.0 Hz and J 11.6Hz), 6.89 (2 H, d, J 6.4 Hz) and 7.26 (2 H, d, J 6.0 Hz); LCMS[M+H]⁺=523.

The table below represents all compounds made with derivatives at the2-position. TABLE 1 Intermediates for synthesis of Galactitol Library.

No. R1* R2* Molecular Ion No. R1 R2 Molecular Ion 17 R1a R2d [M + H]⁺ =537 35 R1f R2a [M + H]⁺ = 508 18 R1a R2c [M + Na]⁺ = 423 36 R1g R2d [M +H]⁺ = 465 19 R1a R2a [M + H]⁺ = 451 37 R1g R2c [M + H]⁺ = 351 20 R1a R2b[M + H]⁺ = 537 38 R1g R2a [M + H]⁺ = 379 21 R1b R2d [M + H]⁺ = 565 39R1g R2b [M + H]⁺ = 465 22 R1b R2c [M + H]⁺ = 451 40 R1h R2d [M + H]⁺ =552 23 R1b R2a [M + H]⁺ = 479 41 R1h R2c [M + H]⁺ = 438 24 R1c R2d [M +H]⁺ = 656 42 R1h R2a [M + H]⁺ = 466 25 R1c R2c [M + H]⁺ = 542 43 R1h R2b[M + H]⁺ = 552 26 R1c R2a [M + H]⁺ = 570 44 R1i R2d [M + H]⁺ = 523 26R1d R2d [M + H]⁺ = 656 45 R1i R2c [M + Na]⁺ = 431 28 R1d R2c [M + H]⁺ =542 46 R1i R2a [M + H]⁺ = 437 29 R1d R2a [M + H]⁺ = 570 47 R1i R2b [M +H]⁺ = 523 30 R1e R2d [M + H]⁺ = 613 48 R1j R2d [M + H]⁺ = 523 31 R1e R2c[M + H]⁺ = 499 49 R1j R2c [M + H]⁺ = 409 32 R1e R2a [M + H]⁺ = 527 50R1j R2a [M + H]⁺ = 437 33 R1f R2d [M + H]⁺ = 594 51 R1j R2b [M + H]⁺ =523 34 R1f R2c [M + H]⁺ = 480*Sidearms for Tables 1 and 2 can be found at the end of Table 2.

2-d. Preparation of Derivatives Reduced at the C-4 Position

Compounds 52 to 86 were prepared according to General Method 13.

TABLE 1 Observed molecular ions of reduced azides

No. R1 R2 Molecular Ion No. R1 R2 Molecular Ion 52 R1a R2d [M + H]⁺ =511 70 R1f R2a [M + H]⁺ = 482 53 R1a R2c [M + H]⁺ = 397 71 R1g R2d [M +H]⁺ = 439 54 R1a R2a [M + H]⁺ = 425 72 R1g R2c No Data 55 R1a R2b NoData 73 R1g R2a [M + H]⁺ = 353 56 R1b R2d [M + H]⁺ = 539 74 R1g R2b [M +H]⁺ = 439 57 R1b R2c [M + H]⁺ = 425 75 R1h R2d [M + H]⁺ = 526 58 R1b R2a[M + H]⁺ = 453 76 R1h R2c [M + H]⁺ = 412 59 R1c R2d [M + H]⁺ = 588 77R1h R2a [M + H]⁺ = 440 60 R1c R2c [M + H]⁺ = 474 78 R1h R2b [M + H]⁺ =526 (loss of acetate) 61 R1c R2a [M + H]⁺ = 502 79 R1i R2d [M + H]⁺ =497 (loss of acetate) 62 R1d R2d [M + H]⁺ = 588 80 R1i R2c [M + H]⁺ =383 63 R1d R2c [M + H]⁺ = 474 81 R1i R2a [M + H]⁺ = 411 (loss ofacetate) 64 R1d R2a [M + H]⁺ = 544 82 R1i R2b [M + H]⁺ = 497 65 R1e R2d[M + H]⁺ = 587 83 R1j R2d [M + H]⁺ = 497 66 R1e R2c [M + H]⁺ = 431 84R1j R2c [M + H]⁺ = 383 (loss of acetate) 67 R1e R2a [M + H]⁺ = 501 85R1j R2a [M + H]⁺ = 411 68 R1f R2d [M + H]⁺ = 568 86 R1j R2b [M + H]⁺ =497 69 R1f R2c [M + H]⁺ = 454Sidearms for Example 2: Tables 1 and 2.

2-e. Final N-Acylation of Galactitol Derivatives in the C-4 Position

Compounds 87 to 416 were prepared in an automated fashion usingchemistries according to General Method 9. As required, protectinggroups on the sidearms, or the ring were hydrolytically cleaved ineither a base or acid catalysed fashion, using either General Method 14or 15.

TABLE 3 Library of 1,5-Anhydro-galactitol Compounds

Compound Retention HPLC No. R1 R2 R3 Yield Time (mins) Method 87 R1a R2aR3a 70 4.72 A 88 R1a R2a R3b 83 4.28 A 89 R1a R2a R3c 74 4.90 A 90 R1aR2a R3d 38 4.44 A 91 R1a R2a R3e 10 4.73 A 92 R1a R2a R3f 44 4.53 A 92R1b R2a R3b 64 4.73 A 94 R1b R2a R3g 77 4.35 A 95 R1c R2a R3h 82 5.33 A96 R1d R2a R3a 50 4.28 A 97 R1d R2a R3c 42 4.00 A 98 R1d R2a R3d 85 4.46A 99 R1d R2a R3f 21 4.62; A 100 R1d R2a R3h 84 4.55 A 101 R1d R2a R3a100 4.56 A 102 R1d R2a R3b 91 4.72 A 103 R1d R2a R3c 70 4.64 A 104 R1dR2a R3d 92 5.27 A 105 R1d R2a R3f 50 4.73 A 106 R1e R2a R3i 100 3.54 A107 R1e R2a R3i 61 4.53 A 108 R1e R2a R3b 97 5.74 A 109 R1e R2a R3d 936.02 A 110 R1e R2a R3e 10 6.18 A 111 R1e R2a R3f 62 5.74 A 112 R1f R2aR3b 80 4.55 A 113 R1f R2a R3d 36 5.17 A 114 R1g R2a R3j 100 4.55 A 115R1g R2a R3k 96 5.36 A 116 R1g R2a R3l 100 6.66 A 117 R1g R2a R3m 1007.01 A 118 R1g R2a R3n 100 6.39 A 119 R1g R2a R3o 97 4.44 A 120 R1g R2aR3o 95 4.37 A 121 R1g R2a R3p 90 5.40 A 122 R1f R2a R3j 90 4.92 A 123R1f R2a R3k 93 5.14 A 124 R1f R2a R3n 96 6.84 A 125 R1f R2a R3n 95 7.19A 126 R1f R2a R3o 72 6.48 A 127 R1f R2a R3q 63 2.60 A 128 R1h R2a R3l 794.07 A 129 R1h R2a R3m 77 3.52 A 130 R1h R2a R3n 100 4.09 A 131 R1h R2aR3o 54 5.36 A 132 R1h R2a R3q 74 5.50 A 133 R1h R2a R3p 91 3.78 A 134R1i R2a R3m 79 4.05 A 135 R1i R2a R3r 77.5 1.50 A 136 R1i R2a R3s 693.77 A 137 R1i R2a R3t 100 5.26 A 138 R1i R2a R3n 93 5.38 A 139 R1i R2aR3v 71 3.83 A 140 R1i R2a R3m 87 4.79 A 141 R1i R2a R3n 95 5.65 A 142R1i R2a R3r 78 5.08 A 143 R1j R2a R3s 81 5.65 A 144 R1j R2a R3t 98 5.27A 145 R1j R2a R3n 93 5.08 A 146 R1i R2a R3v 99 4.92 A 147 R1b R2a R3m 904.92 A 148 R1b R2a R3n 45 5.10 A 149 R1b R2a R3r 97 5.17 A 150 R1b R2aR3s 89 5.19 A 151 R1b R2a R3t 82 5.54 A 152 R1b R2a R3n 95 5.63 A 153R1b R2a R3v 62 6.39 A 154 R1a R2b R3b 95 6.73 A 155 R1a R2b R3d 100 7.49A 156 R1b R2b R3b 97 6.37 A 157 R1b R2b R3d 97 5.00 A 158 R1c R2b R3w16.5 7.47 A 159 R1c R2b R3b 98.5 5.27 A 160 R1c R2b R3d 99 5.01 A 161R1c R2b R3g 40 4.09 A 162 R1d R2b R3b 70.5 4.72 A 163 R1d R2b R3d 695.74 A 164 R1d R2b R3g 95 5.19 A 165 R1e R2b R3w 80 4.62 A 166 R1e R2bR3b 100 4.28; A 167 R1e R2b R3d 100 4.62 A 168 R1e R2b R3g 63 4.28 A 169R1f R2b R3d 97 4.44 A 170 R1f R2b R3j 100 4.37 A 171 R1f R2b R3k 91 4.62A 172 R1f R2b R31 97 4.18 A 173 R1f R2b R3m 65 4.07 A 174 R1f R2b R3x 914.64 A 175 R1f R2b R3g 54 4.99 A 176 R1h R2b R31 85 6.94 A 177 R1h R2bR3k 100 6.09 A 178 R1h R2b R31 100 4.92 A 179 R1h R2b R3m 92 4.53 A 180R1h R2b R3x 90 5.19 A 181 R1i R2b R3m 83 4.61 A 182 R1i R2b R3p 15 1.69A 183 R1i R2b R3r 100 4.09 A 184 R1i R2b R3s 100 1.69; A 185 R1i R2b R3t96 4.18 A 186 R1i R2b R3u 100 4.46 A 187 R1i R2b R3v 100 4.94 A 188 R1iR2b R3m 97 1.71 A 189 R1i R2b R3p 98 1.69 A 190 R1i R2b R3r 84 2.07 A191 R1j R2b R3s 100 2.26 A 192 R1i R2b R3t 100 1.69 A 193 R1i R2b R3u 702.26 A 194 R1i R2b R3v 100 1.6 A 195 Ru R2b R3g 100 3.00 A 196 R1a R2cR3w 100 4.41 A 197 R1a R2c R3a 50 0.55 A 198 R1a R2c R3b 96 1.78 A 199R1a R2c R3c 58 1.69 A 200 R1a R2c R3d 95 2.35 A 201 R1a R2c R3f 32 2.26A 202 R1a R2c R3g 6 4.14 A 203 R1b R2c R3b 100 3.94 A 204 R1b R2c R3d100 4.75 A 205 R1b R2c R3f 32 4.9 A 206 R1b R2c R3i 83 1.8 A 207 R1c R2cR3w 77 1.69 A 208 R1c R2c R3a 44 2.17 A 209 R1c R2c R3b 99 4.33 A 210R1c R2c R3c 43 2.26 A 211 R1c R2c R3d 93 3.34 A 212 R1d R2c R3c 94 4.18A 213 R1d R2c R3d 90 5.36 A 214 R1d R2c R3e 15 2.17 A 215 R1d R2c R3f 911.89 A 216 R1e R2c R3i 100 1.78 A 217 R1e R2c R3w 97 4.55 A 218 R1e R2cR3a 80 6.20 A 219 R1e R2c R3b 94 3.25 A 220 R1e R2c R3c 62 4.09 A 221R1e R2c R3d 91 4.35 A 222 R1e R2c R3f 37 4.48 A 223 R1f R2c R3b 100 4.83A 224 R1f R2c R3d 96 5.28 A 225 R1g R2c R3j 100 1.78 A 226 R1g R2c R3k100 4.00 A 227 R1g R2c R3l 100 4.00 A 228 R1g R2c R3m 100 5.74 A 229 R1gR2c R3x 100 3.73 A 230 R1g R2c R3o 100 5.10 A 231 R1g R2c R3g 100 4.09 A232 R1g R2c R3p 98 5.56 A 233 R1g R2c R3r 95 6.55 A 234 R1f R2c R3j 886.39 A 235 R1f R2c R3k 85 5.13 A 236 R1f R2c R3l 89 4.78 A 237 R1f R2cR3m 94 3.82 A 238 R1f R2c R3x 84 4.09 A 239 R1f R2c R3o 98 3.08 A 240R1f R2c R3q 98 3.54 A 241 R1f R2c R3p 94 3.73 A 242 R1h R2c R3j 100 3.91A 243 R1h R2c R3k 86 5.36 A 244 R1h R2c R3l 98 4.83 A 245 R1h R2c R3m 962.35 A 246 R1h R2c R3x 100 5.28 A 247 R1f R2c R3r 88 5.13 A 248 R1h R2cR3o 97 4.78 A 249 R1h R2c R3q 98 4.88 A 250 R1h R2c R3p 98 4.53 A 251R1h R2c R3q 100 4.68 A 252 R1i R2c R3m 91 4.73 A 253 R1i R2c R3p 1004.88 A 254 R1i R2c R3s 98 4.73 A 255 R1i R2c R3t 82 5.37 A 256 R1i R2cR3u 100 6.50 A 257 R1i R2c R3v 52 5.18 A 258 R1i R2c R3m 92 5.23 A 259R1j R2c R3p 98 5.03 A 260 R1j R2c R3r 4 5.18 A 261 R1j R2c R3s 100 5.28A 262 R1j R2c R3t 94 5.13 A 263 R1j R2c R3u 100 5.0;0 A 264 R1j R2c R3v100 6.39 A 265 R1j R2c R3g 71 4.99 A 266 R1b R2c R3m 100 4.83 A 267 R1bR2c R3p 98 6.50 A 268 R1b R2c R3r 100 4.92 A 269 R1b R2c R3s 63 5.14 A270 R1b R2c R3t 95 6.84 A 271 R1b R2c R3u 91 7.19 A 272 R1b R2c R3v 956.48 A 273 R1b R2d R3i 55 2.60 A 274 R1b R2d R3w 11 3.52 A 275 R1b R2dR3a 48 3.75 A 276 R1b R2d R3b 48 5.36 A 277 R1b R2d R3d 85 5.50 A 278R1b R2d R3e 11 3.78 A 279 R1b R2d R3f 46 4.05 A 280 R1f R2d R3i 73 1.50A 281 R1f R2d R3w 21 3.77 A 282 R1f R2d R3b 81 5.26 A 283 R1f R2d R3d 915.38 A 284 R1f R2d R3f 78 3.83 A 285 R1g R2d R3j 100 4.79 A 286 R1g R2dR3k 100 5.65 A 287 R1g R2d R3l 100 5.08 A 288 R1g R2d R3m 100 5.65 A 289R1g R2d R3o 100 5.27 A 290 R1g R2d R3r 100 5.08 A 291 R1f R2d R3j 724.92 A 292 R1f R2d R3l 100 5.08 A 293 R1f R2d R3x 28 5.10 A 294 R1f R2dR3o 25 5.17 A 295 R1f R2d R3r 100 5.19 A 296 R1h R2d R3k 72 5.54 A 297R1j R2d R3p 56 5.63 A 298 R1j R2d R3r 66 5.10 A 299 R1j R2d R3t 42 6.73A 300 R1j R2d R3u 100 7.49 A 301 R1j R2d R3v 100 6.37 A 302 R1b R2d R3r5 5.00 A 303 R1b R2d R3u 100 7.47 A 304 R1c R2a R3b 100 5.27 A 305 R1eR2a R3w 88 4.72 A 306 R1a R2a R3y 64 4.61 A 307 R1b R2a R3h 95 1.69 A308 R1b R2a R3w 13 4.09 A 309 R1b R2a R3a 76 1.69 A 310 R1b R2a R3f 594.18 A 311 R1c R2a R3y 90 4.46 A 312 R1e R2a R3z 84 4.94 A 313 R1f R2aR3i 100 1.71 A 314 R1f R2a R3w 72 1.69 A 315 R1f R2a R3a 64 2.07 A 316R1f R2a R3e 82 2.26 A 317 R1f R2a R3f 98 1.69 A 318 R1i R2a R31 42 2.26B 319 R1i R2a R32 78 1.60 B 320 R1j R2a R32 56 3.00 B 321 R1a R2b R33 704.41 A 322 R1a R2b R3f 90 0.55 A 323 R1b R2b R3w 94 1.78 B 324 R1b R2bR3c 69 1.69 B 325 R1b R2b R3e 12 2.35 B 326 R1d R2b R3i 98 2.26 B 327R1d R2b R3z 78 4.14 A 328 R1d R2b R3w 82 2.33 B 329 R1e R2b R3z 66 4.75A 330 R1e R2b R3c 81 4.9 B 331 R1f R2b R3i 100 1.8 B 332 R1f R2b R3w 911.69 B 333 R1f R2b R3c 93 2.17 B 334 R1a R2c R3z 52 4.33 A 335 R1b R2cR3i 98 2.26 B 336 R1b R2c R3a 28 3.34 B 337 R1d R2c R3z 60 4.18 A 338R1e R2c R3z 23 4.73 A 339 R1f R2c R3i 100 2.17 B 340 R1f R2c R3z 87 1.89A 341 R1f R2c R3c 100 2.35 B 342 R1f R2c R3f 48 4.55 B 343 R1b R2d R3s50 6.20 A 344 R1a R2b R3i 22 3.25 A 345 R1a R2b R3w 100 4.09 A 346 R1aR2c R3e 34 4.35 A 347 R1b R2a R3e 53 4.48 A 348 R1f R2a R3c 76 1.78 A349 R1b R2b R3i 85 1.48 B 350 R1b R2b R3a 19 1.78 B 351 R1c R2a R3g 415.74 A 352 R1d R2a R3w 80 3.73 A 353 R1h R2d R3x 46 5.13 A 354 R1b R2aR3d 62 5.00 A 355 R1i R2b R32 53 1.41 B 356 R1j R2b R32 75 1.67 B 357R1b R2b R32 41 1.72 B 358 R1b R2b R3m 52 4.88 A 359 R1b R2b R3r 84 4.49A 360 R1b R2b R3s 64 5.57 A 361 R1b R2b R3t 63 6.87 A 362 R1b R2b R3u100 7.13 A 363 R1b R2b R3v 51 6.44 A 364 R1i R2c R32 100 59 B 365 R1jR2c R32 42 3.36 B 366 R1b R2c R32 60 4.1 A 367 R1j R2d R32 7 4.14 A 368R1b R2d R32 25 4.53 A 369 R1a R2e R3c 87 4.26 A 370 R1c R2e R3a 85 4.46A 371 R1h R2e R3o 53 4.73 A 372 R1i R2e R3v 100 5.57 A 373 R1k R2b R3b25 5.19 A 374 R1l R2b R3b 95 5.28 A 375 R1l R2b R3d 100 5.38 A 376 R1mR2b R3d 50 4.73 A 377 R1n R2b R3k 53 4.55 A 378 R1k R2c R3b 72 5.36 A379 R1k R2c R3d 54 5.56 A 380 R1k R2c R3u 74 7.68 A 381 R1b R2f R3i 474.48 A 382 R1b R2f R3b 90 5.68 A 383 R1b R2f R3d 84 5.78 A 384 R1f R2fR3i 69 4.28 A 385 R1f R2f R3b 83 5.58 A 386 R1f R2f R3d 89 5.68 A 387R1g R2f R3m 45 5.68 A 388 R1f R2f R3o 66 5.48 A 389 R1f R2f R3p 32 5.27A 390 R1h R2f R3k 59 6.28 A 391 R1h R2f R31 91 5.65 A 392 R1h R2f R3p 975.82 A 393 R1h R2f R3r 97 5.01 A 394 R1j R2f R3m 81 5.28 A 395 R1j R2fR3p 91 5.78 A 396 R1j R2f R3t 92 6.78 A 397 R1j R2f R3u 99 7.33 A 398R1j R2f R3v 100 6.63 A 399 R1b R2f R3p 89 5.91 A 400 R1b R2f R3s 82 6.18A 401 R1b R2f R3t 100 7.03 A 402 R1b R2f R3u 88 7.83 A 403 R1i R2b R3i54 4.4 A 404 R1d R2e R31 70 3.82 A 405 R1i R2a R3c 39 4.46 B 406 R1i R2cR3z 69 4.18 A 407 R1f R2f R33 21 10.48 A 408 R1h R2f R3m 58 5.58 A 409R1h R2f R3x 92 5.60 A 410 R1i R2f R3g 73 6.2 A 411 R1b R2f R3m 46 5.68 A412 R1k R2b R3r 50 5.14 A 413 R1k R2b R3s 54 6.05 A 414 R1k R2b R3t 88.57.15 A 415 R1k R2b R3u 100 7.35 A 416 R1k R2b R3v 100 6.79 AFunctional Groups for Table 3 Galactitol Library

HPLC Methods for Compounds in Table 3.

Method A

Time H₂O % MeCN % Flow rate ml/min 0 100 0 2 2 100 0 2 10 40 60 2 12 0100 2

Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80Å)

LC Mobile Phase: Acetonitrile: Water 0.1% formic acid

Method B

Time H₂O % MeCN % Flow rate ml/min 0 100 0 2 1 100 0 2 7 65 35 2 8 0 1002 9 0 100 2Agilent SB Zorbax Phenyl 4.6×150 mm (5 μm)LC Mobile Phase: Acetonitrile: Water 0.1% formic acid¹H-NMR Data for Three Compounds of Final Library.

δ_(H) (400 MHz; CDCl₃) 1.01 (3 H, t, J 7.0 Hz), 2.49 (2H expected), 2.95(1 H, t, J 10.9 Hz), 3.30-3.80 (6 H expected), 3.90 (1 H, m), 4.00 (1 H,dd, J 10.6 Hz and J 5.4 Hz), 4.63 (1 H, br. s), 4.75 (1 H, dd, J 9.4 Hzand J 3.4 Hz), 6.00 (1 H, d, J 6.4 Hz), 6.16 (1 H, t, J 5.8 Hz), 7.55 (1H, t, J 7.8 Hz), 8.02 (2 H, t, J 6.4 Hz), 8.25 (1 H, d, J 10.0 Hz) and8.33 (1 H, d, J 1.2 Hz).

δ_(H) (400 MHz; CDCl₃) 0.94 (3 H, t, J 7.0 Hz), 1.07 (2 H, t, J 6.8 Hz),2.30-2.40 (4 H expected), 2.49 (2 H expected), 2.60-3.00 (4 H expected),3.30-3.85 (4 H expected), 3.91-4.10 (2 H, m), 4.44 (1 H, dd, J 9.8 Hzand J 4.2 Hz), 4.49 (1 H, br. s), 6.57 (2 H, m), 6.75 (2 H, dd, J 8.6 Hzand J 1.8 Hz), 7.02 (1 H, t, J 7.7 Hz), 7.66 (2 H, d, J 8.4 Hz), 7.78 (2H, dd, J 14.8 Hz and J 8.4 Hz), 8.22 (1 H, q, J 11.6 Hz and J 5.6 Hz),9.2 (1 H, s) and 9.94 (1 H, d, J9.2 Hz).

δ_(H) (400 MHz; CDCl₃) 2.30-2.90 (6 H expected), 3.05-3.46 (7 Hexpected), 3.59 (2 H, m), 3.80 (2 H, m), 3.93 (1 H, m), 4.21 (1 H, dd, J8.8 Hz and J 4.4 Hz), 4.49 (1 H, t, J 6.0 Hz), 4.77 (1 H, d, J 4.8 Hz),6.64 (1 H, dd, J 6.4 Hz and J 2.0 Hz), 6.87 (1 H, m), 6.98 (2 H, dd, J8.6 Hz and J 2.6 Hz), 7.20 (2 H, dt, J 5.4 Hz and J 2.2 Hz), 7.74 (1 H,dd, J 20.4 Hz and J 9.2 Hz), 8.34 (1 H, t, J 5.6 Hz), 9.11 (1 H, d, J11.6 Hz) and 9.60 (1 H, br. s).

EXAMPLE 3 Synthesis of a1,5-anhydro-2-azido-3-O-benzoyl-6-O-(t-butyldiphenylsilyl)-2-deoxy-D-glucitol

3-a. General Method 8; 3-b. General Method 17; 3-c. General Method 4;3-d. General Method 5; 3-e. General method 18; 3-f. General Method 19.EXAMPLE 4 Synthesis of a1,5-anhydro-2-azido-3-O-benzoyl-6-O-(t-butyldiphenylsilyl)-2-deoxy-D-glucitol

4-a. O— and N-Deprotection of Glucitol Building Block 6 to form Glucitol423.

Compound 423 was synthesised according to General Method 16, 87.2% yield(0.837 g). [M+H]⁺=282.30; 98% Purity by ELSD.

4-b. Formation of 2-Deoxy-2-Azido Glucitol Building Block 5 fromBuilding Block 423

The formation of building block 5 was carried out according to theprocedure described in General Method 17; [M+H]⁺=308.1; 98% purity byELSD. R_(t)=4.62 mins (Agilent SB Zorbax C18 4.6×50 mm (5 ρm, 80Å), LCMobile Phase: Acetonitrile: Water 0.1% formic acid). Gradient asfollows: Time (min) water % CH₃CN % Flow ml/min 0.00 90.0 10.0 1.5001.00 90.0 10.0 1.500 7.00 0.0 100.0 1.500 12.00 0.0 100.0 1.500 20.000.0 100.0 1.500

4-c. Preparation of Building Block 421 from Building Block 5 in ThreeSteps

Compound 421 was subjected to conditions as described in General Method18. Then the product of this reaction was directly subjected to theconditions as described in General Method 3. Finally the material wassubjected to the conditions as described in General Method 19 to provide5 as a white solid in 69% yield after purification; [M+H]⁺=294.6.

R_(t)=3.52 mins, (Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80Å) LC MobilePhase: Acetonitrile: Water 0.1% formic acid) Gradient as follows;Time(min) water % CH₃CN % Flow ml/min 0.00 90.0 10.0 2.00 1.00 90.0 10.02.00 7.00 0.0 100.0 2.00 12.00 0.0 100.0 2.00 13.00 90.0 10.0 2.00 15.0090.0 10.0 2.00

4-d. Silyl Protection of Building Block 421 to form Building Block 422

Compound 422 was formed according to the procedure described in GeneralMethod 19 in 87% yield, [M+H]⁺=532.3; 100% purity by ELSD Rt=6.84 mins,(Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80Å) LC Mobile Phase:Acetonitrile: Water 0.1% formic acid) Gradient as follows: Time(min)water % CH₃CN % Flow ml/min 0.00 90.0 10.0 2.00 1.00 90.0 10.0 2.00 7.000.0 100.0 2.00 14.00 0.0 100.0 2.00 15.00 90.0 10.0 2.00

Spectral analysis for compound 422; ¹H-NMR (CDC3, 400 MHz): 0.99 (s, 9H), 2.99 (d, J=3.76 Hz, 1 H), 3.21 (t, J =11.1, 11.5 Hz, 1 H), 3.31-3.34 (m, 1 H), 3.65-3.72 (m, 1 H), 3.75-3.82 (m, 1 H), 3.82 - 3.89 (m,2 H), 4.02 (dd, J =5,4, 11.5 Hz, 1 H), 5.11 (t, J=9.2, 9.7 Hz, 1 H),7.28-7.43 (m, 8 H), 7.51-7.55 (m, 1 H), 7.58-7.56 (m, 2 H), 8.02-8.06(m, 2 H).

EXAMPLE 5 General Synthetic Route for Preparation of a Library ofGlucitol Peptide Mimetics

5-a. Coupling of Glucitol Building Block 422 to the TrichloroacetimidateDerivatised Wang Resin to Provide 424

Building Block-Resin Conjugate was prepared according to the procedureoutlined in General Method 20.

5-b. Removal of the Benzoyl Group to Form 425

Compounds represented by no. 424 were prepared according to GeneralMethod 21.

5-c. Alkylation at Position 3 of Conjugate 425 to Provide Resin-BuildingBlock 426

The compounds represented by no. 425 were subjected to the conditions asdescribed in General Method 22 to provide compounds no. 426.

5-d. Removal of TBDPS Group

The resins designated by 426 were subjected to the conditions asdescribed in General Method 23.

5-e. Alkylation at Position 6 to Provide

The resin bound compounds designated by 427 were alkylated in groups asdescribed for General Method 22.

5-f. Reduction of Azido Group to Provide

The resin bound compounds designated by 428 were subjected to theconditions as described in General Method 24.

5-g. N-Acylations

The resins designated by 429 were either subjected to the conditions asdescribed in General Method 25: Method 1, or, were subjected to theconditions as described in General Method 22: Method 2.

5-h. Reduction of the Nitro Group

If required, the substituent nitro group of a side-aim was reduced tothe amine according to the procedure described in General Method 26.

5-i. Deprotection of the Fmoc Protecting Group

If required, the Fmoc protecting group on side-arms was deprotectedaccording to the procedure described in General Method 27.

5-i. Guanylation of Amino Group

If required, amino group substituents of side-arms were guanylatedaccording to the procedure described in General Method 28.

5-k. Cleavage of Final Products from the Resins

The final products were cleaved from resin according to the proceduredescribed in General Methods 29. Final compounds were purified byHPLC-MS (See Table 4).

5-l. Hydrolysis of Me Ester

If required, the cleavage mixtures designated by 431 were individuallytreated with a solution of LIOH (0.5 molar) in MeOH/water (1/1) (ph-14)for a week. The solvents were removed in vacuo and the residue waspurified by HPLC. TABLE 4 Library of Glucitol compounds

Comp. Purity¹ Yield Yield² No. R1 R2 R3 M + H (%) Rt mg % 432 R1a R2aR3a 509.1 85.8 3.71 14.1 53.9 ELSD 433 R1c R2b R3b 507.2 63.6 UV 3.384.9 18.7 434 R1d R2b R3c 555.2 77.9 UV 4.04 14.1 435 R1d R2b R3d 541.13.62 8.6 30.9 436 R1a R2c R3a 369.1 73.2 0.86 9.6 50.5 ELSD 437 R1b R2cR3c 453.2 80-UV 3.18 438 R1b R2c R3d 439.1 2.52 1.6 7.1 439 R1e R3b R3a487.1 63.8-UV 2.55 12.9 51.6 440 R1f R3b R3a 446.1 65-UV 2.39 3.6 15.7¹UV implies purity by Ulta-Violet detection, ELSD implies purity byElectron Light Scattering Detection.²Yield calculated for the whole solid phase sequence; 140 mg of resinwas used for preparation of each compound; the substitution was 0.368mmol/g, thus the amount of the starting material was 0.0515 mmol.Side Chains for Table 4:

HPLC Method for Compounds in Table 4:

(Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80Å) LC Mobile Phase:

Acetonitrile: Water 0.1% formic acid) Gradient as follows: Time(min)water % CH3CN % Flow ml/min 0.00 95.0 5.0 2.00 1.00 95.0 5.0 2.00 7.000.0 100.0 2.00 12.00 0.0 100.0 2.00 13.00 95.0 5.0 2.00 15.00 95.0 5.02.00

EXAMPLE 7 Allitol Building Block Synthesis

7-a. Synthesis of a 3-O-Triflate Glucitol 441

Compound 419 (300 mg, 1.08 mmol) and symmetric collidine (0.22 mL, 1.65mmol) were dissolved in anhydrous DCM (7.0 mL) and the solution thencooled to −25° C. A solution of trifluoromethanesulphonic anhydride(0.27 ml, 1.65 mmol) in DCM (2.77 ml) was injected into the solution andthe reaction allowed to proceed overnight. The Solution was reduced todryness, the residue dissolved in DCM (15 ml) and then washed with 0.5molar HCl. The organic phase was dried over MgSO₄, filtered and thesolvent removed in vacuo to provide the product 441 (399 mg, 90.3%).

7b. Inversion at the C-3 Position of a Glucitol Block to Form AllitolBlock 442

To a solution of compound 441 (4.089 mmol) in DMF (7 mL) was added asolution of LiOBz (1.794 mmol) in DMF (7 mL). The reaction was wasallowed to proceed at room temperature overnight. The solvent wasremoved in vacuo and the resulting residue redissolved in EtOAc. Thesolution was then washed with H₂O, the organic layer was collected,dried over MgSO₄, filtered and the solvent removed in vacuo to provideallitol block 442 (74.1% yield).

7c. Cleavage of the Benzylidene Ring System to Provide Allitol Block 443

Compound 443 was prepared according to the procedure as described inGeneral Method 18.

7d. Formation of the Differentially Protected 1,5-Anhydro AllitolBuilding Block

Compound 444 was prepared according to the procedure as described byGeneral Method 19. TABLE 5 Analytical Data for Intermediates and FinalCompound in the Synthesis of Allitol Buildino Block 444.

Observed. Comp. R1 R2 R3 R4 R5 Mass + H 441 N3 H OTf Benzylidene 410.13442 N3 OBz H Benzylidene 352.15 443 N3 OBz H H H 294.12 444 N3 OBz H HTBDPS 532.15

EXAMPLE 8 Prototype Library using H-Allose Building Block

8-a. Coupling of Allitol Building Block 444 to the TrichloroacetimidateDerivatised Wang Resin to Provide 445

Building Block-Resin Conjugate was prepared according to the procedureoutlined in General Method 20.

8-b. Removal of the Benzoyl Group to Form 446

Compound 446 was prepared from precursor 445 according to General Method21.

8-c. Alkylation at Position 3 of Conjugate 446 to Provide Resin-BuildingBlock 447

The compound represented by 446 were subjected to the conditions asdescribed in General Method 22 to provide compounds no. 447.

8-d. Removal of TBDPS Group

The resins designated by 447 were subjected to the conditions asdescribed in General Method 23.

8-e. Alkylation at Position 6

The resin bound compounds designated by 448 were alkylated in groups asdescribed for General Method 22.

8-f. Reduction of Azido Group

The resin bound compounds designated by 449 were subjected to theconditions as described in General Method 24.

8-g. N-Acylations

The resins designated by 450 were either subjected to the conditions asdescribed in General Method 25: Method 1, or, were subjected to theconditions as described in General Method 25: Method 2.

8-h. Reduction of the Nitro Group

If required, the substituent nitro group of a side-arm was reduced tothe amine according to the procedure described in General Method 26.

8-i. Deprotection of the Fmoc Protecting Group

If required, the Fmoc protecting group on side-arms was deprotectedaccording to the procedure described in General Method 27.

8-i. Guanylation of Amino Group

If required, amino group substituents of side-arms were guanylatedaccording to the procedure described in General Method 28.

8-k. Cleavage of Final Products from the Resins (14-Final Product)

The final products were cleaved from resin according to the proceduredescribed in General Methods 29 to provide compounds designated by no.452. Final compounds were purified by HPLC-MS. TABLE 6 Structural andAnalytical Data for Allitol Based Buildina Block Intermediates and FinalProducts

Exp. Mol Compound R1 R2 R3 R4 M + H 453 N3 Bz H TBDPS 532.27 454 N3 H HTBDPS 428.20 455 N3 p-Clbenzyl H TBDPS 552.25 456 N3 p-Clbenzyl H H314.1  457 N3 p-Clbenzyl H p-ClBenzyl No Data 458 N3 p-Clbenzyl H2-Napthyl 454.27 459 NH2 p-Clbenzyl H p-ClBn 412.20 460 NH2 p-Clbenzyl H2-Napthyl 428.20 461 R1a p-Clbenzyl H p-ClBn 691.40 462 R1a p-Clbenzyl H2-Napthyl 707.40 463 R1a p-Clbenzyl H 4-MeBiphenyl 733.42 464 R1bp-Clbenzyl H p-ClBn 719.40 465 R1b p-Clbenzyl H 2-Napthyl 735.50 466 R1bp-Clbenzyl H 4-MeBiphenyl 747.44 452a R1c p-Clbenzyl H p-ClBn 469.26452b R1c p-Clbenzyl H 2-Napthyl 485.32 452c R1d p-Clbenzyl H p-ClBn497.26 452d R1d p-Clbenzyl H 2-Napthyl 513.37 452f R1e p-Clbenzyl Hp-ClBn 511.28 452g R1e p-Clbenzyl H 2-Napthyl 527.33 452h R1f p-ClbenzylH p-ClBn 539.31 4521 R1f p-Clbenzyl H 2-Napthyl 555.38 452j R1gp-Clbenzyl H 4-Mebiphenyl 525.30 452k R1c p-Clbenzyl H 4-Mebiphenyl511.20Sidearms for Table 6

EXAMPLE 9 Synthesis of a1,5-anhydro-3-azido-6-O-(t-butyldimethylsilyl)-2,3-dideoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H, 5H)-troxopyrmidin-5-ylidene) methylamino]-D-allitol

9-a. Formation of a Aminoallitol Building Block From a GlucitolPrecursor

Compound 5 was reacted according to the procedure described in GeneralMethod 6.

9-b. Formation of a Silyl Protected Building Block

Compound 453 was reacted according to the procedure described in GeneralMethod 18. The product of this reaction was reacted according to theprocedure described in General Method 19 to provide compound 454.

EXAMPLE 10 Synthesis of a1,5-anhydro-3-azido-4-O-benzoyl-2,3dideoxy-2-[(1,3-dimethyl-2,4,6-(1H,3H, 5H)-trioxopyrimidin-5ylidene)methylaminol-6-O-(4-methoxybenzyl)-D-gulitol

10-a. General Method 2; 10-b. General Method 3; 10-c. General Method 4;10-d. General Method 6; 10-e. General Method 33; 10-f. General Method 5;10-g. General Method 14.

EXAMPLE 11 Synthesis of a Library of Compounds by Solid Phase TechniquesUsing a Galactitol Building Block

11-a. General Method 14; 11-b. General Method 20; 11-c. General Method21; 11-d. General Method 22; 11-e. General Method 32; 11-f. GeneralMethod 25; 11-g. General Method 24; 11-h. General Method 25; 11-i to lselected from General Methods 26-29 (as appropriate).

EXAMPLE 12 Solid Phase Synthesis of a 2,5-Bis Amino-Allitol Library

12-a. General Method 20; 12-b. General Method 23; 12-c. General Method22; 12-d. General Method 32; 12-e. General Method 25; 12-f. GeneralMethod 24; 12-g. General Method 25; 12-h to k selected from GeneralMethods 26-29 (as appropriate).

EXAMPLE 13 Synthesis of a Library of Compound by Solid Phase TechniquesUsing a Diamino Gulitol Based Building Block

13-a. General Method 20; 13-b. General Method 21; 13-c. General Method22; 13-d. General Method 31; 13-e. General Method 25; 13-f. GeneralMethod 24; 13-g. General Method 25; 13-h to k selected from GeneralMethods 26-29 (as appropriate).

EXAMPLE 14 Synthesis of an Exemplary Library 1

PART 1: In this example three different mimetics of three differentpeptide residues (ie. Phe mimetic 1, 2 and 3, Lys mimetic 1, 2 and 3,and Trp mimetic 1, 2 and 3^(§)) maintain their position on the scaffold(Phe=R¹, Lys=R², Trp=R³), but the different mimetics are varied inrelation to one another.

PART 2: further in this example, three different mimetics of threedifferent peptide residues (ie. Phe mimetic 1, 2 and 3, Lys mimetic 1, 2and 3, and Trp mimetic 1, 2 and 3^(§)) are varied in their substitutionpoint around the scaffold, ie. Phe mimetic 1 moves from R¹ to R² to R³,and so on.

TABLE 8 R1 R2 R3 PART 1 Phe mimetic 1 Lys mimetic 1 Trp mimetic 1 Phemimetic 2 Lys mimetic 1 Trp mimetic 1 Phe mimetic 3 Lys mimetic 1 Trpmimetic 1 Phe mimetic 1 Lys mimetic 1 Trp mimetic 2 Phe mimetic 2 Lysmimetic 1 Trp mimetic 2 Phe mimetic 3 Lys mimetic 1 Trp mimetic 2 Phemimetic 1 Lys mimetic 1 Trp mimetic 3 Phe mimetic 2 Lys mimetic 1 Trpmimetic 3 Phe mimetic 3 Lys mimetic 1 Trp mimetic 3 Phe mimetic 1 Lysmimetic 2 Trp mimetic 1 Phe mimetic 2 Lys mimetic 2 Trp mimetic 1 Phemimetic 3 Lys mimetic 2 Trp mimetic 1 Phe mimetic 1 Lys mimetic 2 Trpmimetic 2 Phe mimetic 2 Lys mimetic 2 Trp mimetic 2 Phe mimetic 3 Lysmimetic 2 Trp mimetic 2 Phe mimetic 1 Lys mimetic 2 Trp mimetic 3 Phemimetic 2 Lys mimetic 2 Trp mimetic 3 Phe mimetic 3 Lys mimetic 2 Trpmimetic 3 Phe mimetic 1 Lys mimetic 3 Trp mimetic 1 Phe mimetic 2 Lysmimetic 3 Trp mimetic 1 Phe mimetic 3 Lys mimetic 3 Trp mimetic 1 Phemimetic 1 Lys mimetic 3 Trp mimetic 2 Phe mimetic 2 Lys mimetic 3 Trpmimetic 2 Phe mimetic 3 Lys mimetic 3 Trp mimetic 2 Phe mimetic 1 Lysmimetic 3 Trp mimetic 3 Phe mimetic 2 Lys mimetic 3 Trp mimetic 3 Phemimetic 3 Lys mimetic 3 Trp mimetic 3 PART 2 Lys mimetic 1 Trp mimetic 1Phe mimetic 1 Trp mimetic 1 Phe mimetic 1 Lys mimetic 1 Lys mimetic 2Trp mimetic 1 Phe mimetic 1 Trp mimetic 1 Phe mimetic 1 Lys mimetic 2Lys mimetic 3 Trp mimetic 1 Phe mimetic 1 Trp mimetic 1 Phe mimetic 1Lys mimetic 3 Lys mimetic 1 Trp mimetic 2 Phe mimetic 2 Trp mimetic 2Phe mimetic 2 Lys mimetic 1 Lys mimetic 2 Trp mimetic 2 Phe mimetic 2Trp mimetic 2 Phe mimetic 2 Lys mimetic 2 Lys mimetic 3 Trp mimetic 2Phe mimetic 2 Trp mimetic 2 Phe mimetic 2 Lys mimetic 3 Lys mimetic 1Trp mimetic 3 Phe mimetic 3 Trp mimetic 3 Phe mimetic 3 Lys mimetic 1Lys mimetic 2 Trp mimetic 3 Phe mimetic 3 Trp mimetic 3 Phe mimetic 2Lys mimetic 2 Lys mimetic 3 Trp mimetic 3 Phe mimetic 3 Trp mimetic 3Phe mimetic 3 Lys mimetic 3

^(§)The various scaffold substituents Lys, Phe, and Trp mimetics 1,2 and3, are listed in Table 3 below. It is noted that in some case amineprotection is required, which is typically effected by Boc protection.It is further noted that in some cases an O-linked mimetic is requiredand in other cases an N-linked mimetic is required. In the cases of theO-linked Lys mimetics, the mimetic is coupled as either the para, orthoor meta nitrobenzyl derivative and subsequently reduced to the amine.TABLE 9 Mimetic 1 Mimetic 2 Mimetic 3 Lys (N-linked)

Lys (O-linked)

Phe (N-linked)

Phe (O-linked)

Trp (N-linked)

Trp (O-linked)

EXAMPLE 15 A Gulitol N-Glycoside Building Block

15-a. Ac₂O, NaOAc; 15-b. General Method 34; 15-c. General Method 3;15-d. (a) TBDPS-Cl, 1,2-DCE, imidazole; (b) 2,2-dimethoxy-propane, TsOH,MeCN; 15-e. (a) Benzoylchloride, pyridine, 1,2-DCE, DMAP; (b) MeOH,TsOH, MeCN; 15-f. General Method 4; 15-g. General Methods 13 and 20;General Method 33.

EXAMPLE 16 Synthesis of Glucosyl N-Glycoside Building Block

16-a. General Method 34; 16-b. General Method 3; 16-c. General Method 4;16-d. General Method 5; 16-e. General Method 18; 16-f. General Method19.

EXAMPLE 17 Synthesis of Glucosylamino 2-Deoxy-2-Amino Library

17-a. Synthesis of 2-Deoxy 2-Amino Glycosyl Amine

To a solution of starting material (20.51 mmol) in MeOH/DMF (4:1, 150mL) was added hydrazine hydrate (92.2 mmol) and the reaction mixture wasstirred at room temperature for 1.5 h. The solution was diluted with˜400 mL chloroform, washed with brine, dried over MgSO₄, filtered andthe solvents evaporated. The crude product 457 was directly used for thenext step.

17-b. Synthesis of 2-Deoxy 2-NHDTPM Protected Glycosyl Amine

Compound 458 was formed from reaction of 457 according to the proceduredescribed in General Method 30.

17-c. Synthesis of 2-Deoxy 2-NHDTPM Protected Glycosyl Amine Alkylatedin the 3-Position

Compounds 459 were formed according to the procedure described inGeneral Method 7.

17-d. Reductive Ring Opening of a 2-Deoxy 2-NHDTPM 3-O-Alkyl GlycosylAmine

A solution of a derivative represented by 460 (4.37 mmol) in dry DCM (30mL) was cooled to 0° C. and 44 ml of a 1 molar solution of BH₃ in THF(44 mmol) and 0.43 mL of a 1 molar solution of dibutylboron triflate inDCM (0.43 mmol) were added. The reaction mixture was stirred at 0° C.and 0.1 eq. of Bu₂BOTf repeatedly added at 1 h intervals until t.l.c.(toluene/EtOAc 1:1) showed complete conversion (total of 0.5 eq.BU₂BOTf. The reaction was quenched by the addition of 8 mL Et₃N and 15mL MeOH at 0° C. After evaporation of the solvents the residue was takenup in 350 mL DCM, the solution washed with half saturated brine,filtered over cotton and the solvents evaporated to yield a residuecontaining the product that was directly used in the next step.

17-e. Re-amino Protection of 3-O-Alkyl Glycosyl Amine

Compounds 461 were formed according to the procedure described inGeneral Method 30; 1H-NMR, (CDCl₃): δ 9.92 (dd, 1H, NH, J_(NH,)2=9.7 Hz,J_(NH,)=CH=13.8 Hz), 7.88 (d, 1H, ═CH), 7.75-7.68 (m, 4H, Ar), 735-7.22(m, 5H, Ar), 6.95-6.86 (m, 2H, Ar), 5.08 (d, 1H, NapCH₂, J_(gem)=12.1Hz), 4.86 (d, 1H, PMPCH₂, J_(gem)=10.5 Hz), 4.72 (d, 1H, PMPCH₂),4.71(d, 1H, H-1b, J_(1,2)=9.2 Hz), 4.69 (d, 1H, NapCH₂), 3.95 (dd, 1H,H-6a, J_(gem)=12.2 Hz, J_(5,6a)=1.7 Hz), 3.85-76 (m, 1H, H-6b), 3.81 (s,3H, OMe), 3.74 (dd, 1H, H-4, J_(3,4)=8.9 Hz, J_(4,5)=9.4 Hz), 3.64 (dd,1H, H-3, J_(2,3)=9.3 Hz), 3.49 (ddd, 1H, H-5), 3.22 (s, 3H, NMe), 3.11(dd, 1H, H-2), 3.05 (s, 3H, NMe).

17-f. Methylation of the 6-Position of a Glycosylamine

Compounds 462 were formed according to the procedure described inGeneral Method 7; 1H-NMR (CDCl3); δ 9.92 (dd, 1H, NH, J_(NH2)=9.7 Hz,J_(NH═CH)=13.8 Hz), 7.88 (d, 1H, ═CH), 7.75-7.68 (m, 4H, Ar), 735-7.22(m, 5H, Ar), 6.95-6.86 (m, 2H, Ar), 5.08 (d, 1H, NapCH₂, J_(gem)=12.1Hz), 4.86 (d, 1H, PMPCH₂, J_(gem)=10.5 Hz), 4.72-4.68 (m, 3H, NapCH₂,PMPCH₂, H-1), 3.80-3.74 (m, 3H, H6a, H-6b, H4), 3.81 (s, 3H, OMe), 3.64(dd, 1H, H-3, J_(2,3)=9.3 Hz), 3.49 (ddd, 1H, H-5), 3.22 (s, 3H, NMe),3.11 (dd, 1H, H-2), 3.05 (s, 3H, NMe).

17-g. Removal of the DTPM Group of 2-Deoxy-2-Amino GlycosylamineCompound

Compounds 463 were formed according to the procedure described inGeneral Method 8; 1H-NMR, (CDCl₃) δ 7.78-7.66 (m, 4H, Ar), 7.43-7.32 (m,5H, Ar), 6.86-6.69 (m, 2H, Ar), 5.48 (s, 1H, CH-PMP), 5.05 (d, 1H,NapCH₂, J_(gem)=11.3 Hz), 4.77 (d, 1H, NapCH₂), 4.47 (d, 1H, H-1b,J_(1,2)=8.9 Hz), 4.28 (dd, 1H, H-6a, J_(gem)=10.3 Hz, J_(5,6a)=5.5 Hz),3.76-3.65 (m, 2H, H-6b, H-4), 3.72 (s, 3H, OMe), 3.49 (dd, 1H, H-3,J_(2,3)=9.0 Hz, J_(3,4)=9.0 Hz), 3.46 (ddd, 1H, H-5), 2.75 (dd, 1H,H-2).

17-h. Synthesis of a 2-Deoxy-2-N-Acyl Glycosyl Amine

The compounds 464 were synthesised according to the procedure describedin General Method 31.

17-i. Solution Phase Reduction of an Anomeric Azide

The compounds 465 were synthesised according to the procedure describedin General Method 13.

17-j. Formation of 1-N-Acyl Derivatives of a Glucosaminyl Derivative

The compounds 466 synthesised according to the procedure described inGeneral Method 31.

17-k. Removal of a Boc Protecting Group from a2-Deoxy-2—N-Acyl-Glycosylamine Derivative

Dissolve crude 467 (˜0.21mmol) in 10 mL 20% TFA in DCM and stir at roomtemperature for 10 min. Evaporate solvents and dry the remaining syrupunder high vacuum. Redissolve in DCM and wash with 1M KOH, filter overcotton, evaporate and purify by column chromatography (eluent DCM/MeOH10:1 1% Et₃N) to give the product (for the formation of compounds 469,470, 471). Yield typically 35% over two steps.

17-l. Solution Phase Guanylation (only for the Formation of Compound472)

To a solution of crude 467 (max. 0.22 mmol) in dry DMF were added 89 mg(0.44 mmol) 3,5-dimethylpyrazole-1-carboxamidine nitrate and 84 μL (0.48mmol) DIPEA and the reaction mixture stirred for 3 h. The solvents wereevaporated and the residue dried under high vacuum to give 280 mg of amixture containing the desired product. The purification usingpreparative HPLC gave 8 mg of the pure product 472.

Comp. R1 R2 R3 Molecular Ion 469 naphthyl phenyl H [M + H]⁺ = 522.33 470naphthyl 4-Chlorophenyl H [M + H]⁺ = 556.1 471 naphthyl benzyl H [M +H]⁺ = 536.36 472 4-chlorobenzyl α-naphthyl C(NH)NH₂ [M + H]⁺ = 598.39

EXAMPLE 18 Synthesis of a Carboxamide C-Glycoside 1

Conditions: NaOMe/MeOH; (ii) Acetone, NBS; (iii) trichloroacetonitrle,potassium carbonate, DCM; (iv) TMS-CN, TMS-Off, DCM; (v)NaOH/H₂O₂; (vi)(a) TMS-CH₂N₂; (b) p-methoxybenzaldehyde dimethylacetal, CSA, MeCn, DMF;(vii) (a) LIOH, H₂O, THF; (b) HBTU, DIPEA, DMF, R¹—NH₂; (viii)benzoylchloride, pyridine, 1,2-DCE, DMAP; (TsOH, MeOH, MeCN, H₂O; (x)TBDPS-Cl, imidazole, 1,2-DCE.

EXAMPLE 19 Synthesis of an Ally C-Glycoside

Conditions: (i) Tf₂O, pyridine, DCM; (b) NaN₃, DMF; (ii) acetone, H⁺;(iii) Ac₂O, pyridine; (iv) hexamethyldisilazane, I₂, CH₃—S—S—CH₃; (v)NaOMe/MeOH; (vi) TsOH, α,α-dimethoxytoluene, MeCN; (vii)benzoylchloride, 1,2-DCE, pyridine, DMAP; (viii) TsOH, MeOH, H₂O, MeCN;(ix) TBDPS-Cl, imidazole, 1,2-DCE; (x) TMS-allyl, TMS-OTf, DCM.

EXAMPLE 20 Synthesis of a Range of C-Glycosides

*Ramburg-Backlund rearrangement of phthalimido thioglycosides I to givean exo methylene compound II. The products can them be converted to avariety of C-glycosides which can be further elaborated to buildingblocks as exemplified by 28. The reaction pathway can furnishC-glycosides with a large number of alkyl or aromatic side-chains at theanomeric position. Conditions: (i) Oxone, (ii) KOH, CCl₄, (iii) BH₃,HOOH, H₂/Pd; (iv) H₂Pd; (v) ArX, Pd(0), H₂/Pd; (vi) AcSH, AIBN, H₂/Pd;(vii) (a) KOH, (b) TfN₃, RT, CH₂Cl₂, MeOH, H₂O/cat. CUSO₄, 90%; (viii)α,α-dimethoxytoluene, TsOH, MeCN/MeOH; (ix) BzCl, pyridine, (x)MeOH/MeCN/H₂O, TsOH; (xi) TBDPS-Cl, pyridine.

EXAMPLE 21 Synthesis of an Ribofuranosyl Azide Building Block

21-a. 1-Azido-2,3,5-triacetyl ribose 506

To a solution of 1,2,3,5-tetraacetyl ribose 505 (0.189 mol) in dry DCM(480 ml) at room temperature was added trimethylsilyl azide (0.211 mol)followed by a solution of anhydrous SnCl₄ (9.40 mmol) in dry DCM (60ml). The resulting colourless solution was stirred at room temperatureovernight. The solution was washed with saturated sodium bicarbonate.The combined organic extracts were dried (MgSO₄) and the solvent wasremoved in vacuo to give a colourless oil, 100%.

21-b. 1-Azido ribose 507

The compound was synthesised according to the procedure described inGeneral Method 1 (used directly in the following step).

21-c. 1-Azido-2,3-isopropylidene ribose 508

A solution of 1-azido ribose 507 (0.2 mol) in dry acetone (120 ml) and2,2-dimethoxypropane (488 mmol) at room temperature and under nitrogenwas treated with conc. sulfuric acid (16.9 mmol). The resulting solutionwas stirred at room temperature for 30 min. The reaction was quenchedwith pyridine and the solvent was removed in vacuo. The residue wasdissolved in DCM (500 ml), washed with 10% citric acid and saturatedsodium bicarbonate, dried (MgSO₄) and the solvent was removed in vacuoto give a yellow oil which was purified by a squat column on silica gel(20-40% EtOAc/petrol) to give a yellow oil 508, 69 % from tetraacetate505. δ_(H) (400 MHz: CDCl₃) 1.32 (s, 3H, CH₃), 1.50 (s, 3H, CH₃), 2.31(dd, J 8.0, 5.2 Hz, 1H, OH), 3.67 (ddd, J 12.4, 7.6, 4.8 Hz, 1H, H5a),3.77 (ddd, J 12.4, 6.2, 4.0 Hz, 1H, H5b), 4.41 (dd, J 5.2, 4.8 Hz, 1H,H4), 4.52 (d, J 6.0 Hz, 1H, H3), 4.77 (d, J 6.0 Hz, 1H, H2), 5.54 (s,1H, H1).

21 -d. 1 -Azido-2,3-isopropylidene-5′-mesylate ribose 509

Methanesulfonyl chloride (18.1 mmol) was added over one min. to asuspension of the 2,3-isopropylidene ribose 508 (16.5 mmol) in drypyridine (11 ml) at 0° C. and under N₂. The resulting suspension wasstirred at 0° C. for 2.5 h, then quenched with water (20 ml) andextracted with ethyl acetate (2×20 ml). The combined organic extractswere washed with 10% citric acid and saturated NaHCO₃, dried (MgSO₄),and the solvent was removed in vacuo to give a pale yellow oil which waspurified by a squat column on silica gel (20-40% EtOAc/petrol) to give awhite solid, 88%. LCMS: >90% by ELSD, (M−N₃)⁺251. δ_(H) (400 MHz: CDCl₃)1.31 (s, 3H, CH₃), 1.49 (s, 3H, CH₃), 3.09 (s, 3H, SO₂CH₃), 4.28 (dd, J10.6, 6.8 Hz, 1H, H5a), 4.30 (dd, J 10.6, 6.0 Hz, 1H, H5_(b)), 4.50 (td,J 6.1, 1.2 Hz, 2H, H3, H4), 4.72 (dd, J 6.0, 1.3 Hz, 1H, H2), 5.56 (s,1H, H1).

21-e. 1-Azido-2,3-isopropylidene-5′-phthalimido-ribose 510

A suspension of sugar derivative 509 (14.3 mmol), potassium phthalimide(18.8 mmol) and sodium iodide (2.86 mmol) in DMF (105 ml) was heated at100° C. for 30 min., then cooled to room temperature and diluted withwater (500 ml) and cooled in an ice-water bath. The resulting productwere collected by vacuum filtration, washed with water and dried overP₂O₅ in a dessicator overnight as white crystals, 51%. LCMS: >95% byELSD, (2M+H)⁺711. δ_(H) (400 MHz: CDCl₃) 1.29 (s, 3H, CH₃), 1.45 (s, 3H,CH₃), 3.91 (dd, J 13.9, 8.4 Hz, 1H, H5_(a)), 3.95 (dd, J 13.9, 6.5 Hz,1H, H5_(b)), 4.57 (t, J 6.4 Hz, 2H, H3, H4), 4.78 (d, J 5.8 Hz, 1H, H2),5.57 (s, 1H, H1), 7.73 (d, J 3.2 Hz, 1H, ArH), 7.74 (d, J 3.2 Hz, 1H,ArH), 7.87 (d, J 3.2 Hz, 1H, ArH), 7.88 (d, J 3.2 Hz, 1H, ArH).

21-f. 1-Azido-2,3-isopropylidene-5′-amino-ribose 511

A suspension of sugar derivative 510 (8.13 mmol) in methanol (21 ml) wastreated with hydrazine hydrate (12.0 mmol) to give a pale yellowsolution which was heated at reflux for 2 h. The methanol was removed invacuo from the resulting suspension and the residue was dissolved inwater (40 ml) and acidified (to pH 1) with conc. HCl. The resultingprecipitate was removed by vacuum filtration and washed with water. Tothe filtrate was added solid sodium hydroxide (to pH 10) and the productwas extracted with CHCl₃ and dried (MgSO₄). The solvent was removed invacuo to give a yellow oil, 93%. LCMS: (M−N₃)⁺=172; δ (400 MHz: CDCl₃)1.32 (bs, 5H, CH₃, NH₂), 1.50 (s, 3H, CH₃), 2.84 (dd, J 13.1, 6.0 Hz,1H, H5_(a)), 2.90 (dd, J 13.0, 8.1 Hz, 1H, H5_(b)), 4.24 (t, J 7.0 Hz,1H, H4), 4.48 (d, J 5.8 Hz, 1H, H3), 4.61 (d, J 4.8 Hz, 1H, H2), 5.53(s, 1H, H1).

REFERENCES

-   1. K. C. Nicolaou; J. M. Salvino, K. Raynor; S. Pietranico; T.    Reisine; R. M. Freidinger, R. Hirschmann, Pept: Chem., Struct Biol.,    Proc. Am. Pept. Symp., 11^(th), 1990-   2. (a) H. Kunz, T. Wundberg, C. Kallus, T. Opatz, S. Henke, W.    Schmidt, Angew. Chem. Int. Ed., 1998, 37, No. 18, (b) K. Kallus, T.    Wundberg, W. Schmidt, S. Henke, H. Kunz, Tet. Lett., 40, 1999,    7783-7786, (c) U. Hünger, T. Maidhof, O. Knöll, H. Kunz, Poster    Presentation, 20^(th) International Carbohydrate Symposium,    Hamburg-Germany, (d) T. Opatz, C. Kallus, T. Wundberg, W.    Schmidt, S. Henke, H. Kunz, Poster Presentation, 20^(th)    Intemational Carbohydrate Symposium, Hamburg-Germany.-   3. R. Hirschmann, K. C. Nicolaou, S. Pietramico, J. Salvino, E. M.    Lealy, W. C. Shakepeare, P. S. Spengler, P. Hamley, A. B. Smith, T.    Reisine, K. Raynor, C. Donaldson, W. Vale, L. Maechler, R. M.    Freidinger, C. D. Strader, J. Am. Chem. Soc., 1993, 115, 12550

1. A compound of formula I

Wherein, n is 0 or 1; R1 is selected from the group consisting ofhydrogen or —N(Z)Y wherein; When R1 is —N(Z)Y, then: R6 and R7 arehydrogen; Y is selected from hydrogen, or the following, where G denotesthe point of connection to the nitrogen atom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting ofsubstituted or unsubstituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl,heteroaryl, arylalkyl and heteroarylalkyl of 1 to 20 atoms, The groupsX1 are independently selected from the group consisting of substitutedor unsubstituted alkyl, alkenyl, alkynyl, heteroalkyl, acyl, arylacyl,heteroarylacyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl of 1 to20 atoms, at least one of the groups R2, R3, R4 and R5 is selected fromthe group consisting of —OX2 or —N(T)Y, and the others of the groups R2,R3, R4 and R5 are independently selected from hydrogen, —OH, —OX2,—N(T)Y, wherein Y is as defined above, T is selected from hydrogen orX2; and X2 is independently selected from substituted or unsubstitutedalkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl orheteroarylalkyl of 1 to 20 atoms, With the provisos that: a. X2 may notbe another carbohydrate ring, a cyclitol ring or contain anothercarbohydrate ring, b. all of the X2 substituents may not be the same;When R1 is H, R6 and R7 are hydrogen, or together form a carbonyloxygen; at least two of the groups R2, R3, R4 and R5 are selected fromthe group consisting of —OX2 or —N(T)Y, and the others are independentlyselected from hydrogen, —OH, —OX2, —N(T)Y, wherein Y is as definedabove, T is selected from hydrogen or X2; and X2 is independentlyselected from substituted or unsubstituted alkyl, alkenyl, alkynyl,heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20atoms, With the provisos that: c. X2 may not be another carbohydratering, a cyclitol ring or contain another carbohydrate ring, d. all ofthe X2 substituents may not be the same.
 2. The compound of claim 1,wherein wherein the ring is selected from the pyran or furan form andthe anomeric center is selected from the α or β configuration.
 3. Thecompound of claim 1, wherein the groups Z and Y are combined to form amonocyclic or bicyclic ring structure of 4 to 10 atoms.
 4. The compoundof claim 3, wherein the ring structure is further substituted with X1groups.
 5. The compound of claim 1 in wherein W is substituted with amoiety selected from the group consisting of OH, NO, NO₂, NH₂, N₃,halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid.
 6. The compound of claim 1 inwherein X1 is substituted with a moiety selected from the groupconsisting of OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile,alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acidester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate and hydroxamic acid.
 7. Thecompound of claim 1, wherein Y is hydrogen.
 8. The compound of claim 1in wherein X2 is substituted with a moiety selected from the groupconsisting of OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile,alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acidester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate and hydroxamic acid.
 9. Thecompound of claim 1 wherein at least three of the groups R2, R3, R4 andR5 are selected from —OX2 or —N(T)Y;
 10. The compound of claim I whereinR1 is hydrogen.
 11. The compound of claim 10 wherein independently atleast one of R2, R3, R4, or R6 is —N(T)Y, and at least one is —OX2. 12.The compound of claim 10 wherein independently at least two of R2, R3,R4, or R6 are —OX2.
 13. The compound of claim 10 wherein at least two ofR2, R3, R4, or R6 is —N(T)Y.
 14. The compound of claim 1 wherein R1 is—N(Z)Y.
 15. The compound of claim 14 wherein at least one of R2, R3, R4,or R6 is —N(T)Y.
 16. The compound of claim 14 wherein at least two ofR2, R3, R4, or R6 is —N(T)Y.
 17. The compound of claim 14 wherein atleast two of R2, R3, R4, or R6 are —OX2.
 18. A method of synthesis ofcompounds of claim 10, wherein n is 1, comprising the step of reducing asynthetic intermediate of formula III, in which V is bromine orchlorine, R6 and R7 are hydrogen, or together form a carbonyl oxygen,R5, R4, R3, and R2 are selected from the group consisting of OH, O-acyl,N₃, NHDde, NHDTPM, NHZ, NHBOC, phthalimide, OX2, N(T)Y and anO-protecting group, X2 is independently selected from alkyl, alkenyl,alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of1 to 20 atoms, T is hydrogen or X2, Y is selected from hydrogen, or thefollowing, where G denotes the point of connection to the nitrogen atomin N(T)Y;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms,


19. The method of claim 18, wherein R6 and R7 together form a carbonyloxygen and R5 is O-alkyl, O-arylalkyl or O-aryl.
 20. The method of claim19, wherein the R5 substituent is substituted with a moiety selectedfrom the group consisting of OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂,CH₂F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid,carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl,heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl,aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate,sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,hydroxamic acid.
 21. The method of claim 18, wherein the O-protectinggroups comprise acetals and ketals which protect two adjacent oxygens.22. A method of synthesis of compounds according to claim 14, in which nis 1, comprising the step of reacting a compound of formula III with anazide nucleophile, to form an anomeric azide and reduction of theanomeric azide to form an anomeric amine and reaction of the anomericamine with an electrophile.
 23. A method of combinatorial synthesis ofcompounds of claim 1, wherein n is 1, comprising the step ofimmobilizing a compound of formula IV onto a support.

wherein R6 and R7 are hydrogen, or together form a carbonyl oxygen; R1is selected from the group consisting of hydrogen; —N(Z)Y and —C(Z)Ywherein; When R1 is —N(Z)Y, then: Y is selected from hydrogen, or thefollowing, where G denotes the point of connection to the nitrogen atomin N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, When R1 is —C(Z)Y, then: Y isselected from the group consisting of two hydrogen atoms, a doublebonded oxygen (═O) to form a carbonyl, and a triple bonded nitrogen toform a nitrile, Z is absent, or is selected from hydrogen or U, WhereinU is selected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, R5, R4, R3, and R2 are selected fromthe group consisting of OH, O-acyl, N₃, NHDde, NHDTPM, NHZ, NHBOC,phthalimide, OX2, N(T)Y and an O-protecting group, and the linkagebetween the compound of formula IV and the support is through any one ofpositions R1, R2, R3, R4 or R5, X2 is independently selected from alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl orheteroarylalkyl of 1 to 20 atoms, T is hydrogen or X2, Y is selectedfrom hydrogen, or the following, where G denotes the point of connectionto the nitrogen atom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms,
 24. The method of claim 23 whereinthe support is selected from the group consisting of derivatisedpolystyrene, tentagel, wang resin, MBHA resin, aminomethytpolystyrene,rink amide resin DOX-mpeg, and polyethylene glycol.
 25. A method ofsynthesis of compounds according to claim 13, in which n is 0,comprising the step of reacting a compound of formula V in the presenceof a lewis acid with an azide source to form an anomeric azide,reduction of the anomeric azide to form an anomeric amine and reactionof the anomeric amine with an electrophile.

in which V is —OAcyl, R6 and R7 are hydrogen, or together form acarbonyl oxygen, R4, R3, and R2 are selected from the group consistingof OH, O-acyl, N₃, NHDde, NHDTPM, NHZ, NHBOC, phthalimide,OX2, N(T)Y andO-protecting group, X2 is independently selected from alkyl, alkenyl,alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of1 to 20 atoms, T is hydrogen or X2, Y is selected from hydrogen, or thefollowing, where G denotes the point of connection to the nitrogen atomin N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms,
 26. The method of claim 25,wherein R6 and R7 together form a carbonyl oxygen, and R4 is substitutedO-alkyl, O-arylalkyl or O-aryl.
 27. A method of combinatorial synthesisof compounds of claim 1, wherein n is 0, comprising the step ofimmobilizing a compound of formula VI onto a support,

Wherein R1 is selected from the group consisting of hydrogen; —N(Z)Y and—C(Z)Y wherein; When R1 is —N(Z)Y, then: Y is selected from hydrogen, orthe following, where G denotes the point of connection to the nitrogenatom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, When R1 is —C(Z)Y, then: Y isselected from the group consisting of two hydrogen atoms, a doublebonded oxygen (═O) to form a carbonyl, and a triple bonded nitrogen toform a nitrile, Z is absent, or is selected from hydrogen or U, WhereinU is selected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, R6 and R7 are hydrogen, or togetherform a carbonyl oxygen, R4, R3, and R2 are selected from the groupconsisting of OH, O-acyl, N₃, NHDde, NHDTPM, NHZ, NHBOC, phthalimide,OX2, N(T)Y and O-protecting group, X2 is independently selected fromalkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl orheteroarylalkyl of 1 to 20 atoms, T is hydrogen or X2, Y is selectedfrom hydrogen, or the following, where G denotes the point of connectionto the nitrogen atom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, and the linkage between thecompound of formula VI and the support is through any one of positionsR1, R2, R3, or R4.
 28. The method of claim 27, wherein the support isselected from the group consisting of derivatised polystyrene, tentagel,wang resin, MBHA resin, aminomethylpolystyrene, rink amide resinDOX-mpeg,and polyethylene glycol.
 29. A method of solution phasecombinatorial synthesis of compounds of claim 1, comprising the step ofalkylating a free hydroxyl on a compound of formula IV or formula VI,wherein R6 and R7 are hydrogen, or together form a carbonyl oxygen; R1is selected from the group consisting of hydrogen; —N(Z)Y and —C(Z)Ywherein; When R1 is —N(Z)Y, then: Y is selected from hydrogen, or thefollowing, where G denotes the point of connection to the nitrogen atomin N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, When R1 is —C(Z)Y, then: Y isselected from the group consisting of two hydrogen atoms, a doublebonded oxygen (═O) to form a carbonyl, and a triple bonded nitrogen toform a nitrile, Z is absent, or is selected from hydrogen or U, WhereinU is selected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, R5, R4, R3, and R2 are selected fromthe group consisting of OH, O-acyl, N₃, NHDde, NHDTPM, NHZ, NHBOC,phthalimide, OX2, N(T)Y and an O-protecting group, X2 is independentlyselected from alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl,arylalkyl or heteroarylalkyl of 1 to 20 atoms, T is hydrogen or X2, Y isselected from hydrogen, or the following, where G denotes the point ofconnection to the nitrogen atom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, and any one of the protectingsubstituents may be removed prior to alkylation.
 30. A compound offormula I

Wherein, n is 0 or 1; R6 and R7 are hydrogen, or together form acarbonyl oxygen; R1 is selected from the group consisting of hydrogen;—N(Z)Y and —C(Z)Y wherein; When R1 is —N(Z)Y, then: Y is selected fromhydrogen, or the following, where G denotes the point of connection tothe nitrogen atom in N(Y)Z;

Z is selected from hydrogen or X1; Q is selected from hydrogen or W; Thegroups W are independently selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, The groups X1 are independentlyselected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyland heteroarylalkyl of 1 to 20 atoms, When R1 is —C(Z)Y, then: Y isselected from the group consisting of two hydrogen atoms, a doublebonded oxygen (═O) to form a carbonyl, and a triple bonded nitrogen toform a nitrile, Z is absent, or is selected from hydrogen or U, WhereinU is selected from the group consisting of alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl andheteroarylalkyl of 1 to 20 atoms, When R1 is H, at least two of thegroups R2, R3, R4 and R5 are selected from the group consisting of —OX2or —N(T)Y, and the others are independently selected from hydrogen, —OH,—OX2, —N(T)Y, wherein Y is as defined above, T is selected from hydrogenor X2; and X2 is independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20atoms, When R1 is N(Z)Y or C(Z)Y, at least one of the groups R2, R3, R4and R5 are selected from the group consisting of —OX2 or —N(T)Y, and theothers are independently selected from hydrogen, —OH, —OX2, —N(T)Y,wherein Y is as defined above, T is selected from hydrogen or X2; and X2is independently selected from alkyl, alkenyl, alkynyl, heteroalkyl,aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms, Withthe provisos that: a X2 may not be another carbohydrate ring, a cyclitolring or contain another carbohydrate ring, b all of the X2 substituentsmay not be the same, and c when R1 is C(Z)Y, and Z is C═O and R5 isN(T)Y, both T and Y may not be hydrogen, or Y may not be an amino acidor peptide.